Facultad de Ciencias de la Salud

Línea del Conocimiento de Estructura y Función

Sistema Endocrino
y Reproductor
ME148
Semana 07
2018-02
Facultad de Ciencias de la Salud
Línea del Conocimiento de Estructura y Función

UNIDAD IV:
HOMEOSTASIS DE LA GLUCOSA

FISIOPATOLOGÍA DE LA
HOMEOSTASIS DE LA GLUCOSA

Semana 07
LOGRO DE LA UNIDAD

Al finalizar la unidad el estudiante describe

las principales características estructurales
y funcionales de los órganos relacionados
con el metabolismo energético y explica los
efectos de la disfunción de las hormonas
respectivas.
TEMARIO
A GLUCAGÓN
• Célula productora
• Factores estimulantes e inhibidores de la secreción
• Acciones

B SOMATOSTATINA
• Célula productora
• Factores estimulantes e inhibidores de la secreción
• Acciones

C FISIOPATOLOGÍA DE LA INSULINA
• Diabetes Mellitus I y II
• Criterios diagnósticos de diabetes
• Hipoglicemia
PÁNCREAS

Pancreatic regulation of glucose homeostasis. PV Röder et al

Experimental & Molecular Medicine (2016) 48, e219
GLUCAGÓN

Sintetizado y liberado por las células alfa del páncreas.

Las acciones del glucagón antagonizan a la insulina
El tejido diana principal del glucagón es el hígado donde sus
acciones son mediadas por  AMPc.
SECRECIÓN DE GLUCAGÓN

I. Una reducción de la
concentración de
glucosa en sangre
II. Un aumento de la
concentración sérica
de arginina y alanina

III. La estimulación de
sistema nervioso
simpático
EFECTOS EN EL METABOLISMO DE
CARBOHIDRATOS
RÁPIDO:
1. Aumenta la liberación de glucosa a la circulación al estimular la
glucosa – 6 – fosfatasa hepática.

2. Aumenta la degradación de glucógeno (glucogenólisis) al activar la

glucógeno fosforilasa hepática.
*** En ayuno la glucosa obtenida por glucogenólisis en músculo
esquelético está inducida por catecolaminas NO por glucagón. Esta
glucosa NO se libera a la circulación, es utilizada por el propio tejido.

A LARGO PLAZO:

3. Aumenta la gluconeogénesis hepática al activar una enzima clave:

fosfoenolpiruvato carboxikinasa (PEPCK)
4. Disminuye la concentración de fructosa 2,6 bifosfato; esto favorece
la gluconeogénesis.
EFECTOS EN EL METABOLISMO DE
LIPIDOS

Aumenta:

1. La degradación de triglicéridos (lipólisis) hepática al

aumentar la actividad de la lipasa sensible a hormonas de
stress. Esta acción ocurre sólo a nivel hepático y no a nivel
de tejido adiposo.

2. La formación de cuerpos cetónicos (cetogénesis) como el  -

hidroxibutirato y acetoacetato en el hígado.

Inactiva:
3. La Acetil- CoA carboxilasa por lo que disminuye la conversión
de acetil CoA a malonil CoA. La disminución de la
concentración de malonil CoA favorece la cetogénesis sobre
la lipogénesis.
EFECTOS EN EL METABOLISMO DE
PROTEÍNAS

1. Se favorece la degradación proteica (proteólisis);

por consiguiente los niveles urea aumentan en
sangre.

2. Disminución de masa magra corporal

** Si bien el glucagón favorece la proteólisis, las hormonas

responsables de un tasa de degradación proteica elevada
en ayuno son principalmente catecolaminas y cortisol.
SOMATOSTATINA

Secretada por las células delta

de los islotes pancreáticos

Acciones:

•Inhibir a glucagón
•Inhibir a insulina
INSULINA Y GLUCAGÓN

Pancreatic regulation of glucose homeostasis. PV Röder et al

Experimental & Molecular Medicine (2016) 48, e219
INSULINA Y GLUCAGÓN
INSULINA Y HORMONAS
CONTRARREGULADORAS
Interrelación Multisistémica para Regular la Homeostasis
de la Glucosa

Pancreatic regulation of glucose homeostasis. PV Röder et al

Experimental & Molecular Medicine (2016) 48, e219
Es una enfermedad
metabólica que se
caracteriza por hiperglicemia
asociada a defectos en la
secreción de insulina, la
acción de la insulina o
ambos.
 DM2: LA PUNTA DEL ICEBERG

Estadio III DM2

Estadio II Glucosa plasmática

post-alimentos Microangiopatía
Tolerancia Macroangiopatía
disminuida a la Producción de
glucosa glucosa
Transporte de
glucosa
Deficiencia secreción de insulina
Estadio I Aterogénesis
Tolerancia Lipogénesis
Obesidad TG
normal a la Hiperinsulinemia
glucosa HD
Relación Resistencia a la
cintura/cadera insulina L
Hipertensión
Genes de la Diabetes arterial

Matthaei S. et al. Endocrine Reviews 21:585-618, 2000, adaptado de Beck-Nielsen and

Groop
Octeto Ominoso

Lancet 2011; 378: 169–81

 Classification of Diabetes

1. Type 1 diabetes
– β-cell destruction
2. Type 2 diabetes
– Progressive insulin secretory defect
3. Gestational Diabetes Mellitus (GDM)
4. Other specific types of diabetes
– Monogenic diabetes syndromes
– Diseases of the exocrine pancreas, e.g., cystic fibrosis
– Drug- or chemical-induced diabetes
American Diabetes Association Standards of Medical Care in Diabetes.
Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
 Criteria for the Diagnosis of Diabetes

Fasting plasma glucose (FPG)

≥126 mg/dL (7.0 mmol/L)
OR
2-h plasma glucose ≥200 mg/dL
(11.1 mmol/L) during an OGTT
OR
A1C ≥6.5%
OR
Classic diabetes symptoms + random plasma glucose
≥200 mg/dL (11.1 mmol/L)
American Diabetes Association Standards of Medical Care in Diabetes.
Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
 Prediabetes*

FPG 100–125 mg/dL

(5.6–6.9 mmol/L): IFG
OR

2-h plasma glucose 140–199 mg/dL (7.8–11.0

mmol/L): IGT
OR

A1C 5.7–6.4%
* For all three tests, risk is continuous, extending below the lower limit of a
range and becoming disproportionately greater at higher ends of the range.
American Diabetes Association Standards of Medical Care in Diabetes.
Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
 Risk factors for Prediabetes and T2D

www.diabetes.org/are-you-at-risk
American Diabetes Association Standards of Medical Care in Diabetes.
Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
DIABETES MELLITUS I

• Destrucción de la células beta

pancreáticas.
• Etiología: autoinmune

• Hiperglicemia
• ↑ gluconeogénesis
• ↑ ácidos grasos libres por lipólisis
• ↑ síntesis de cetoácidos
• Acidosis metabólica
• ↑ aminoácidos en plasma por
catabolismo proteico ↑

• Tratamiento:
Inyección exógena de insulina
 Recommendations: Pharmacologic Therapy For Type 1 Diabetes

• Most people with T1DM should be treated with

multiple daily injections of prandial insulin and
basal insulin or continuous subcutaneous insulin
infusion (CSII). A

• Individuals who have been successfully using

CSII should have continued access after they
turn 65 years old. E

American Diabetes Association Standards of Medical Care in Diabetes.

Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
Recommendations: Pharmacological Therapy For Type 1 Diabetes (2)

• Consider educating individuals with T1DM on

matching prandial insulin dose to carbohydrate
intake, premeal blood glucose, and anticipated
activity. E

• Most individuals with T1DM should use insulin

analogs to reduce hypoglycemia risk. A

American Diabetes Association Standards of Medical Care in Diabetes.

Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
 Pramlintide
• FDA approved for T1DM
• Amylin analog
• Delays gastric emptying, blunts pancreatic
glucose secretion, enhances satiety
• Induces weight loss, lowers insulin dose
• Requires reduction in prandial insulin to reduce
risk of severe hypos

American Diabetes Association Standards of Medical Care in Diabetes.

Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
DIABETES MELLITUS I
DIABETES MELLITUS II
• Etiología: Multifactorial

• Resistencia a la insulina con regulación a

la baja de receptores de insulina

• Síntomas: varían. Asintomático al inicio

hasta síntomas similares a DM I: poliurea,
polidisia, polifagia, pérdida de peso.

• Tratamiento:
- Cambio en estilo de vida y la dieta,
ejercicio.
- Farmacológico: sulfonilureas (aumentan
secreción de insulina), biguanidas
(metformina  regula al alza los
receptores de insulina).
SINTOMAS DE DIABETES
TEST TOLERANCIA ORAL A LA GLUCOSA
HEMOGLOBINA GLICOSILADA (HbA1c)
 Mean Glucose Levels for Specified A1C
Levels

Mean Glucose
Mean Plasma Glucose* Fasting Premeal Postmeal Bedtime
A1C% mg/dL mmol/L mg/dL mg/dL mg/dL mg/dL
6 126 7.0
<6.5 122 118 144 136
6.5-6.99 142 139 164 153
7 154 8.6
7.0-7.49 152 152 176 177
7.5-7.99 167 155 189 175
8 183 10.2
8-8.5 178 179 206 222
9 212 11.8
10 240 13.4
professional.diabetes.org/eAG
11 269 14.9
12 298 16.5
American Diabetes Association Standards of Medical Care in Diabetes.
Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
 Recommendations: Prevention or Delay of T2DM

• Patients with prediabetes should be referred to

an intensive diet and physical activity behavioral
counseling program adhering to the tenets of the
DPP targeting a loss of 7% of body weight, and
should increase their moderate physical activity
to at least 150 min/week. A

American Diabetes Association Standards of Medical Care in Diabetes.

Prevention or delay of type 2 diabetes. Diabetes Care 2017; 40 (Suppl. 1): S44-S47
Recommendations: Prevention or Delay of T2DM (2)

• Metformin therapy for prevention of type 2

diabetes should be considered in those with
prediabetes, especially for those with BMI >35
kg/m2, aged < 60 years, women with prior
gestational diabetes (GDM), those with rising
A1C despite lifestyle intervention. A
• Long-term use of metformin may be associated
with biochemical vitamin B12 deficiency, and
periodic measurement of vitamin B12 levels
should be considered in metformin-treated
patients, especially in those with anemia or
peripheral neuropathy. B
American Diabetes Association Standards of Medical Care in Diabetes.
Prevention or delay of type 2 diabetes. Diabetes Care 2017; 40 (Suppl. 1): S44-S47
 Approach to the Management of Hyperglycemia

more A1C less

Patient/Disease Features stringent 7% stringent
Risk of hypoglycemia/drug adverse effects
low high
Disease Duration
newly diagnosed long-standing
Life expectancy
long short
Relevant comorbidities
absent Few/mild severe
Established vascular complications
absent Few/mild severe

Patient attitude & expected

treatment efforts highly motivated, adherent, excellent less motivated, nonadherent, poor
self-care capabilities self-care capabilities

Resources & support system

readily available limited
American Diabetes Association Standards of Medical Care in Diabetes.
Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
 Recommendations: Pharmacologic Therapy For T2DM

• Metformin, if not contraindicated and

if tolerated, is the preferred initial pharmacologic
agent for T2DM. A
• Consider insulin therapy (with or without
additional agents) in patients with newly dx’d
T2DM who are markedly symptomatic and/or
have elevated blood glucose levels (>300
mg/dL) or A1C (>10%). E

American Diabetes Association Standards of Medical Care in Diabetes.

Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
Sitios de acción de los Antidiabéticos
Diabetes Care Volume 39, Supplement 1, January 2016
HIPOGLICEMIA
• Glucosa menor de 70 mg/dL
• Síntomas asociados a hipoglicemia: glucosa < o = 50 mg/dL
 Classification of Hypoglycemia

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
SÍNTOMAS DE HIPOGLICEMIA
 Recommendations: Hypoglycemia
• Individuals at risk for hypoglycemia should be asked
about symptomatic and asymptomatic hypoglycemia at
each encounter. C
• Glucose (15–20 g) preferred treatment for conscious
individual with blood glucose < 70 mg/dL. E
• Glucagon should be prescribed for those at increased
risk of clinically significant hypoglycemia, defined as
blood glucose < 54 mg/dL, so it is available if needed. E
• Hypoglycemia unawareness or episodes of severe
hypoglycemia should trigger treatment re-evaluation. E

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
 Recommendations: Hypoglycemia (2)
• Insulin-treated patients with hypoglycemia unawareness
or an episode of severe hypoglycemia should be advised
to raise glycemic targets to strictly avoid further
hypoglycemia for at least several weeks, to partially
reverse hypoglycemia unawareness, and to reduce risk
of future episodes. A
• Ongoing assessment of cognitive function is suggested
with increased vigilance for hypoglycemia by the
clinician, patient, and caregivers if low cognition and/or
declining cognition is found. B

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
Average
wholesale price
(AWP) does not
necessarily reflect
discounts,
rebates, or other
price adjustments
that may affect
the actual cost
incurred by the
patient but
highlights the
importance of
cost
considerations.
There have
been
substantial
increases in
the price of
insulin in the
past decade,
and cost-
effectiveness is
an important
consideration.
Guidelines

• Full version
• Abridged version for PCPs
• Free app
• Pocket cards with key figures
• Free webcast for continuing
education credit

Professional.Diabetes.org/SOC
Recomendaciones para el curso

• Revisar su material de clase al menos un día antes de

clase
• Organizar los temas de clase en organizadores visuales
(apuntes, esquemas o mapas mentales)
• Apuntar las dudas o preguntas que no lograron resolver
• Participar en clase con preguntas o respuestas
• Dedicación a cada uno de sus cursos
• Dormir y descansar al menos una tarde del fin de
semana