Insulina y dm

TERAPIA DE INSULINA EN
LA DIABETES MELLITUS
DR. LEOPOLDO MELÉNDEZ
RIVERA
MEDICINA INTERNA

INSULINA EN EL DIABÉTICO
• DIABETES TIPO 1
• DIABETES TIPO 2 REFRACTARIA A
TRATAMIENTO ORAL
• DIABETES GESTACIONAL
• SÍNDROMES ESPECÍFICOS

DIABETES CARE 26 S1, 2003

• INSULINA
– ORIGEN
• BOVINA
• PORCINA
• HUMANA
RECOMBINANTE
• ANÁLOGOS

– TIPOS
• RÁPIDA
• CORTA
• INTERMEDIA
• LARGA



NEJM 352;2:174-183, 2005

• MARCAS

– NPH
HUMULIN N (LILLY)
– RÁPIDA
HUMULIN R (LILLY)
– LISPRO
HUMALOG
– GLARGINA
LANTUS
– ASPARTICA
NOVORPID

• TRANSPORTE Y
ALMACENAJE

– REFRIGERADA 4 A 8
– NO AGITAR
– MENOS DE UN MES

• MEZCLADO
– PRIMERO INSULINA
RÁPIDA Y DESPUES
INTERMEDIA
– GLARGINA NO SE
COMBINA

• JERINGAS

– INYECCIÓN
SUBCUTÁNEA
– CAPACIDAD 0.3, 0.5, 1 Y
2 ML
– NO SE COMPARTE

– SUSTITUTOS
• INYECTORES JET
• BOMBAS DE INFUSIÓN
CONTÍNUA


• TÉCNICA DE
INYECCIÓN

– INYECTAR VOLUMEN DE
AIRE EQUIVALENTE
– CARGAR Y AGITAR
GENTIL
– MEZCLAR PRIMERO
INSULNA RÁPIDA
– INYECTAR A 90
– NO ASPIRAR
– NO BURBUJAS

• SITIO DE
INYECCIÓN

– BRAZO
– GLUTEOS
– ABDOMEN
– ESCAPULAS
– MUSLOS


• DOSIS

– INSULINA RÁPIDA 15 MIN PREPRANDIAL O AL
FINAL
– INSULINA INTERMEDIA 30 MIN PREPRANDIAL
– INSULINA LISPRO PREPRANDIAL INMEDIATA
– INSULINA GLARGINA PREPRANDIAL INMEDIATA


• DOSIS

NEJM 352;2:174-183, 2005

• DOSIS
– NPH
• COLACIÓN NOCTURNA

NEJM 352;2:174-183, 2005

• DOSIS
. Recommended Strategies for Initiating Insulin in Type 2 Diabetes*

Therapeutic
A1C Threshold Strategy Suggested Initial Dose† Follow-up

7.0% to 10.0% Initiate basal 10 U every day for insulin glargine Advance insulin dose weekly until FPG is within
despite 2 oral insulin target
medications
Continue oral 10 U every day or twice daily for NPH If A1C remains > 7.0% and PPG is elevated, add
medications prandial insulin starting with largest daily meal

Monitor A1C every 3 months until < 7.0%; every 6
months thereafter

> 10.0% despite 2 Initiate basal- Basal, as above Optimize prandial doses for each meal
oral medications prandial insulin‡

Discontinue oral Prandial: 5-10 U at each meal (Approximately 1 U for Advance insulin dose weekly until PPG and FPG are
secretagogues every 10-15 g of carbohydrate to start) within target

Premixed insulin is not usually recommended, but can Monitor A1C every 3 months until < 7.0%; every 6
consider 10 U before breakfast and dinner months thereafter

FPG = fasting plasma glucose; NPH = neutral protamine Hagedorn; PPG = postprandial glucose
*Consider adding insulin in all patients who have A1C > 7.0% despite optimal doses of 2 oral agents.
†Reduced doses may be prudent in chronic renal disease.

‡A basal insulin can be introduced initially; however, the need to advance within 3-5 months to a basal-prandial regimen is more likely at such baseline A1C levels.

An alternative for initial dosing of prandial insulin is 5-10 U at the main meal.

Medscape General Medicine 7(4):49, 2005

• COMPLICACIONES

– HIPOGLICEMIA


Advantages of Basal-Prandial and Premixed Insulin Regimens[42,56]

Basal-Prandial Insulin Regimens
Prandial Insulin (Rapid-
Acting Analog or Regular
Basal Insulin (Insulin Glargine or NPH) Human) Premixed Insulin Products

Advantages
Flexibility: allows variation in timing of meals Rapid-acting analogs allow Convenience: longer- and
and activities greater flexibility/allow shorter-acting insulins combined
variation in timing of meals and in 1 injection (may be given twice
activities daily)
Easy to titrate based on FPG, A1C Easy to titrate based on PPG,
A1C
Glargine has no pronounced peak and is Can mix with other insulin
associated with a lower incidence of products to reduce number of
hypoglycemia, especially nocturnal injections
hypoglycemia
Glargine provides ~24-hour coverage with
once-daily dosing



Disadvantages of Basal-Prandial and Premixed Insulin Regimens
Basal-Prandial Insulin Regimens Premixed Insulin Products
Basal Insulin (Insulin Glargine or NPH) Prandial Insulin (Rapid-Acting
Analog or Regular Human)

Glargine cannot be mixed with other Greater number of daily Cannot titrate basal insulin
insulins injections and prandial insulin
individually
NPH may require 2 injections per day Less mealtime flexibility Increased risk for
for 24-hour coverage with regular human insulin hypoglycemia
NPH is associated with variability of Lunchtime prandial dose Less mealtime flexibility
absorption (ie, site of injection, inter- may need to be
and intrapatient) administered separately
NPH has an increased risk for Difficult to administer premeal
midmorning and/or nocturnal correction doses, especially
hypoglycemia with prefilled pen cartridges



• RECHAZO

– INYECCIONES
– MITOS
• CEGUERA
• ALERGIAS
• FASE TERMINAL
• AUMENTO DE PESO
• RIESGO
CARDIOVASCULAR


• INSULINA RÁPIDA

– EN CETOACIDOSIS
• BOLO INICIAL DE 0.15 UI/KG
• INFUSIÓN DE 0.1 UI/KG/HR Y DOBLAR CADA HORA

• BOLO INICIAL 0.4 UI/KG
– 50% IV, 50% SC
• BOLO SC 0.1UI/KG/HR Y 10UI SC/HR

• AL ALCANZAR 250 MG/DL…
Diabetes Care 24:131-153, 2001
Diabetes Care 27:S94-S102, 2004

– EN CETOACIDOSIS
• AL ALCANZAR 250 MG/DL (SIN CETOSIS):

– INFUSIÓN A 0.05 UI/KG/HR
– 5 UI SC/HR O 5-10 UI SC/ 2 HR

• AL ALCANZAR 200 MG/DL:

– 5 UI SC C/50 MG >150 MG/DL
– 20 UI SC C/150 MG>300 MG/DL

Diabetes Care 27:S94-S102, 2004

– EN ESTADO HIPEROSMOLAR
• BOLO INICIAL 0.15 UI/KG IV
• INFUSION 0.1 UI/KG/HR
• DOBLAR CADA HORA HASTA BAJAR 50-70 MG/DL
 INICIA 1 UI/HR DOSIS-RESPUESTA
 INFUSIÓN 0.02 UI/KG/HR HASTA 10 – 50 UI/HR

• SIN ESTADO HIPEROSMOLAR
– 5 UI SC C/50 MG >150 MG/DL
– 20 UI SC C/150 MG>300 MG/DL
– 0.05-0.1 UI/KG/HR AL MANTENER 250-300MG/DL

– DEFICIT DE AGUA

• (Na/140 – 1) X 0.6 X PESO
• 150 (1.07) 60 (2.5)

• MIELINOLISIS PONTINA


– OSMOLARIDAD SÉRICA

• 2 Na + glucosa/18 + BUN/2.8
• 150 400 60 343
• 150 100 60 327
• 145 100 60 316
• 145 100 15 3

• Osm Ser = 280 - 310

– EN HIPERGLICEMIA AGUDA

• 1 UI DISMINUYE 30 A 50 MG/DL DE GLUCOSA SÉRICA

– ESQUEMAS SEGÚN ESCALA DE TIRA REACTIVA

• 1 UI METABOLIZA 4 GRAMOS DE GLUCOSA EXÓGENA

– 1000 CC SOL. GLUCOSADA 5% UTILIZA 12.5 UI

GOODMAN Y GILMAN, TRATADO DE FISIOLOGÍA

– EN HIPERGLICEMIA AGUDA

• ESQUEMA DE INSULINA RÁPIDA

– 200-240 MG/DL = 3UI 80-120 MG/DL
– 240-360 MG/DL = 5UI 120-160 MG/DL
– 360-480 MG/DL = 7UI 80-200 MG/DL

• CONDICIONANTES

– OBESIDAD
– FUNCIÓN RENAL
– FUNCIÓN HEPÁTICA
– USO PREVIO
– ESTADO CATABÓLICO

VALORACIÓN PREOPERATORIA, HALABE J.

• INSULINA LISPRO
– EN HIPERGLICEMIA PREPRANDIALES
• 10 - 20% DE LA DOSIS TOTAL DIARIA POR CADA
EVENTO
• PREVIA GLICEMIA CAPILAR UNA HORA ANTES
• APLICAR 0 – 15 MINUTOS ANTES

– EN EVENTOS QUIRÚRGICOS
• 10 – 20% DE LA DOSIS TOTAL CADA 4 HRS PRN
• 0.02 UI/KG CADA HORA

Diabetes Care 27:553-591, 2004:

RESISTENCIA A LA INSULINA
DEFINICIÓN

• REQUERIMIENTO DIARIO >100 UI
• NECESIDAD DE UN MONTO MAYOR DE INSULINA
(ENDÓGENO O EXÓGENA) PARA ALCANZAR LA RESPUESTA
NORMAL

SINÓNIMOS

• SÍNDROME METABÓLICO
• SÍNDROME X
• SÍNDROME DISMETABÓLICO

www.medscape.com/viewprogram/3942, ABRIL 2005

1. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)
Diagnostic Criteria for the Metabolic Syndrome

Diagnosis is made when 3 or more of the following are
present:
Waist circumference
Men > 102 cm
Women> 88 cm

Fasting triglycerides >/= 150 mg/dL

Blood pressure >/= 130/85 mmHg

HDL cholesterol </= 50 mg/dL for women; </= 40 mg/dL for
men
Fasting glucose* >/= 110 mg/dL
•This was changed to 100 mg/dL following the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association (ADA)
conference proceedings[

The value of 110 mg/dL does not reflect the revised ADA criteria for impaired fasting glucose.


2. WHO Criteria for the Metabolic Syndrome

Insulin resistance, as identified by 1 of the following:
• Type 2 diabetes
• Impaired fasting glucose (101-125 mg/dL)
• Impaired glucose tolerance (140-199 mg/dL 2h after 75 g of glucose)
• If normal fasting glucose, glucose uptake below the lowest quartile for background population
under hyperinsulinemic, euglycemic conditions

Plus 2 of the following:
• Antihypertensive medication and/or blood pressure >/= 140 mmHg systolic or >/= 90 diastolic
• Triglycerides >/= 150 mg/dL
• HDL < 35 mg/dL for men or < 39 mg/dL for women
• BMI > 30 kg/m2 and/or waist-hip ratio > 0.9 men, > 0.85 women
• Urinary albumin excretion >/= 20 mcg/min or albumin-creatinine ratio >/= 30 mg/g

3. AACE Clinical Criteria for Diagnosis of the Insulin Resistance Syndrome

Risk Factor Cutoff
Overweight/obesity BMI >/= 25 kg/m2
Elevated triglycerides >/= 150 mg/dL
HDL cholesterol
Men < 40 mg/dL
Women < 50 mg/dL
Blood pressure >/= 130/85 mmHg
2h post 75 g glucose > 140 mg/dL
challenge
Fasting glucose Between 110 and 126 mg/dL
Additional risk factors -Family history of type 2 diabetes
-Hypertension
-Coronary heart disease (CHD)
-Polycystic ovary syndrome
-Sedentary lifestyle
-Advanced age
-Ethnic groups at high risk for type 2 diabetes or
CHD

4. Major Cardiovascular Risk Factors

Hypertension (blood pressure > 140/90 mmHg or taking
antihypertensive medication)
Cigarette smoking
Obesity
Physical inactivity
Dyslipidemia/low HDL cholesterol (< 40 mg/dL) or high triglycerides
( > 150 mg/dL)
Diabetes mellitus (coronary heart disease risk equivalent)
Microalbuminuria or glomerular filtration rate < 60 mL/min
Age ( > 55 years for men, > 65 for women)
Family history of premature coronary heart disease

CAUSAS

• MUTACIONES EN LOS TRANSPORTADORES DE GLUCOSA
• ALTERACIONES EN EL GEN GLUT 4
• DEFECTOS EN LA TRANSLOCACIÓN DEL GEN GLUT 4
• DEFECTOS EN LAS VÍAS DE SEÑALIZACIÓN
• DISMINUCIÓN DEL TRANSPORTE DE GLUCOSA POR INSULINA

NEJM 1999; 341:248-257

CAUSAS

• FACTORES PARACRINOS
•ÁCIDOS GRASOS
•GLUCOTOXICIDAD
•FACTOR DE NECROSIS TUMORAL

• FACTORES NO INSULÍNICOS
• EJERCICIO
• BRADIQUININAS
• ÓXIDO NITROSO
• FACTORES DE CRECIMIENTO INSULINA-LIKE
• PÉPTIDO C
• HORMONAS TIROIDEAS

NEJM 1999; 341:248-257

TRATAMIENTO

METFORMINA DIETA EJERCICIO EDUCACIÓN

DISLIPIDEMIA HIPERTENSIÓN

ASPIRINA MICROALBUMINURIA


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