DIABETES MELLITUS

Medscape Medical News > Psychiatry, Kathleen Louden / Jul 02, 2013
Refined Carbs May Trigger Food Addiction
http://www.medscape.com/viewarticle/807209?nlid=31943_1048&src=wnl_edit_dail

Consumption of a meal that has a high glycemic index (GI) appears to stimulate key
brain regions related to craving and reward, a finding that supports the controversial
hypothesis of food addiction, new research suggests.
After eating the high-GI meal, participants initially had a surge in blood glucose level
that was 2.4-fold higher than after the low-GI meal, followed by a crash in blood
glucose at 4 hours, the authors reported. They also reported excessive hunger 4
hours after the high-GI meal, Dr. Ludwig said.
The results show that highly processed carbohydrates, such as white bread,
potatoes, and concentrated sugar, "alter brain activity in ways that make us crave
them even more," he said.
Asked by Medscape Medical News to comment on the findings, Dr. Gold, who was
not involved with the study, said that the brain imaging test the researchers used "is
exceptional and provides additional strong evidence that manufactured foods, sugar,
and fats can interact with the brain and systems that [also] are hijacked by drugs of
abuse.“ "Hedonic overeating...makes more sense with clinical research like this,"
Dr. Gold, who is professor and chair of psychiatry at UF College of Medicine,
concluded.
 Medscape Medical News > Neurology
Fructose Effects in Brain May Contribute to Overeating, Megan Brooks / Jan 02, 2013
http://www.medscape.com/viewarticle/776988

• Consuming fructose appears to cause changes in the brain

that may lead to overeating, a new study suggests.
• "Increases in fructose consumption have paralleled the
increasing prevalence of obesity, and high-fructose diets are
thought to promote weight gain and insulin resistance," lead
author Kathleen A. Page, MD, and colleagues from Yale
University in New Haven, Connecticut, write.
• In this study, they showed in healthy volunteers that although
glucose ingestion resulted in reduced activation of the
hypothalamus, insula, and striatum on MRI — areas that
regulate appetite, motivation, and reward processing — as
well as increased functional connections between the
hypothalamic striatal network and increased satiety. Fructose
ingestion had none of these effects.
 Glucose vs Fructose
• Fructose ingestion produces smaller increases in circulating satiety
hormones compared with glucose ingestion, and central administration of
fructose provokes feeding in rodents, whereas centrally administered
glucose promotes satiety, the authors write. "Thus, fructose possibly
increases food-seeking behavior and increases food intake.“
• They observed that glucose (but not fructose) ingestion reduced activation
of the hypothalamus, insula, and striatum. Glucose ingestion also increased
functional connections between the hypothalamic-striatal network and
increased ratings of satiety and fullness.
• Brain responses were markedly different after ingestion of an equal amount
of fructose. Not only did fructose fail to diminish hypothalamic activity, but it
also induced a small, transient increase in hypothalamic activity.
• The striatum, as with the hypothalamus, also did not deactivate with
fructose ingestion, which may cause decreased inhibitory responses.
Fructose ingestion was also associated with reduced systemic levels of the
satiety-signaling hormone insulin.
 Appetite Regulation
• "These findings support the conceptual framework that when the
human brain is exposed to fructose, neurobiological pathways
involved in appetite regulation are modulated, thereby promoting
increased food intake," Jonathan Q. Purnell, MD, and Damien A.
Fair, PhD, from Oregon Health & Science University, Portland,
write in an accompanying editorial.
• They say the implications of this study, coupled with mounting
evidence from epidemiologic, metabolic feeding, and animal
studies, are that the "advances in food processing and economic
forces leading to increased intake of added sugar and
accompanying fructose in U.S. society are indeed extending the
supersizing concept to the population's collective waistlines."
http://www.elespectador.com/noticias/salud/el-polemico-comercial-de-bebidas-
azucaradas-sacaron-del-articulo-653715 8 SEP / 2016
 http://www.elespectador.com/noticias/salud/el-polemico-
comercial-de-bebidas-azucaradas-sacaron-del-articulo-653715
8 SEP / 2016

El comercial de televisión, que dura 30 segundos,

arranca con productos que contienen azúcar y
concluye con las posibles consecuencias de su
consumo. Según Martha Sandoval, economista e
investigadora de Educar, la campaña se hizo debido
a una preocupación fundamental por la salud de los
colombianos, “promover los impactos que tienen las
bebidas azucaradas en la salud, en particular,
porque en Colombia el 51 % de la población sufre
de obesidad, el 17 % está relacionado con niños y
peor aún, la tasa anual de muertes por
enfermedades asociadas al consumo de bebidas
azucaradas es de 4.928 personas”, aseguró.
http://www.elespectador.com/noticias/salud/el-polemico-comercial-de-
bebidas-azucaradas-sacaron-del-articulo-653715 8 SEP / 2016
• OMS: La diabetes mellitus es una
enfermedad crónica causada por la
incapacidad del organismo para producir
insulina, o por la falta de efecto de la
hormona producida.

• ADA: La diabetes es un grupo de

enfermedades caracterizadas por un alto
nivel de glucosa resultado de defectos en
la capacidad del cuerpo para producir o
usar insulina.
 DEFINITION AND DESCRIPTION OF DIABETES MELLITUS

Diabetes mellitus is a group of metabolic diseases characterized

by hyperglycemia resulting from defects in insulin secretion, insulin
action, or both. The chronic hyperglycemia of diabetes is associated
with long-term damage, dysfunction, and failure of various organs,
especially the eyes, kidneys, nerves, heart, and blood vessels.

Several pathogenic processes are involved in the development of

diabetes. These range from autoimmune destruction of the cells of the
pancreas with consequent insulin deficiency to abnormalities that result
in resistance to insulin action. The basis of the abnormalities in
carbohydrate, fat, and protein metabolism in diabetes is deficient action
of insulin on target tissues.

Deficient insulin action results from inadequate insulin secretion and/or

diminished tissue responses to insulin at one or more points in the
complex pathways of hormone action.

Impairment of insulin secretion and defects in insulin action frequently

coexist in the same patient, and it is often unclear which abnormality, if
either alone, is the primary cause of the hyperglycemia.
 Etiologic classification of diabetes
mellitus
I.Type 1 diabetes (-cell destruction, usually leading to
absolute insulin deficiency).
A.Immune mediated
B. Idiopathic

II. Type 2 diabetes (may range from predominantly

insulin resistance with relative insulin deficiency to a
predominantly secretory defect with insulin
resistance).

III. Other specific types

IV. Gestational diabetes mellitus (GDM)

 Clasificación de la DM
• DM1.

• DM2.

• Otros tipos específicos de diabetes.

• DM gestacional.
 Etiologic classification of diabetes mellitus
III. Other specific types
• E. Drug- or chemical-induced
• 1. Vacor
• A. Genetic defects of -cell function • 2. Pentamidine
• 1. Chromosome 12, HNF-1 (MODY3) • 3. Nicotinic acid
• 2. Chromosome 7, glucokinase (MODY2) • 4. Glucocorticoids
• 3. Chromosome 20, HNF-4 (MODY1) • 5. Thyroid hormone
• 4. Chromosome 13, insulin promoter factor-1 (IPF-1; • 6. Diazoxide
MODY4) • 7. -adrenergic agonists
• 5. Chromosome 17, HNF-1 (MODY5) • 8. Thiazides
• 6. Chromosome 2, NeuroD1 (MODY6) • 9. Dilantin
• 7. Mitochondrial DNA • 10. -Interferon
• 8. Others • 11. Others
• B. Genetic defects in insulin action • F. Infections
• 1. Type A insulin resistance • 1. Congenital rubella
• 2. Leprechaunism • 2. Cytomegalovirus
• • 3. Others
3. Rabson-Mendenhall syndrome
• G. Uncommon forms of immune-mediated
• 4. Lipoatrophic diabetes diabetes
• 5. Others • 1. “Stiff-man” syndrome
• C. Diseases of the exocrine pancreas • 2. Anti–insulin receptor antibodies
• 1. Pancreatitis • 3. Others
• 2. Trauma/pancreatectomy • H. Other genetic syndromes sometimes
• 3. Neoplasia associated with diabetes
• 4. Cystic fibrosis • 1. Down’s syndrome
• 5. Hemochromatosis • 2. Klinefelter’s syndrome
• • 3. Turner’s syndrome
6. Fibrocalculous pancreatopathy
• 4. Wolfram’s syndrome
• 7. Others
• 5. Friedreich’s ataxia
• D. Endocrinopathies • 6. Huntington’s chorea
• 1. Acromegaly • 7. Laurence-Moon-Biedl syndrome
• 2. Cushing’s syndrome • 8. Myotonic dystrophy
• 3. Glucagonoma • 9. Porphyria
• 4. Pheochromocytoma • 10. Prader-Willi syndrome
• 5. Hyperthyroidism • 11. Other
• 6. Somatostatinoma
• 7. Aldosteronoma
• 8. Others
Monogenic diabetes resulting from mutations that
primarily reduce β-cell function accounts for 1-2%
of diabetes cases, although it is often
misdiagnosed as either type 1 or type 2 diabetes.
Knowledge of the genetic etiology of diabetes
enables more-appropriate treatment, better
prediction of disease progression, screening of
family members and genetic counseling. We
propose that the old clinical classifications of
maturity-onset diabetes of the young ( MODY ) and
permanent neonatal diabetes Mellitus ( PNDm )
are obsolete and that specific genetic etiologies
should be sought in four broad clinical situations
because of their specific treatment implications.
http://www.diabetesgenes.org/
Diabetes diagnosed before 6 months of age frequently results from
mutation of genes that encode Kir6.2 (ATP-sensitive inward rectifier
potassium channel) or sulfonylurea receptor 1 subunits of an ATP-
sensitive potassium channel, and improved glycemic control can be
achieved by treatment with high-dose sulfonylureas rather than insulin.

Patients with stable, mild fasting hyperglycemia detected particularly when

they are young could have a glucokinase mutation and might not require
specific treatment.

Individuals with familial, young-onset diabetes that does not fit with either
type 1 or type 2 diabetes might have mutations in the transcription factors
HNF-1a (hepatocyte nuclear factor 1-α) or HNF-4α, and can be treated with
low-dose sulfonylureas.

Extrapancreatic features, such as renal disease (caused by mutations in

HNF-1β) or deafness (caused by a mitochondrial m.3243A>G mutation),
usually require early treatment with insulin.
 Table 1— Diagnostic thresholds for diabetes and lesser
degrees of impaired glucose regulation
Category TEST
FPG 2-h PG

Normal <100 mg/dl (<5.6 mmol/l) <140 mg/dl (<7.8 mmol/l)

IFG 100–125 mg/dl (5.6–6.9 —

mmol/l)
IGT — 140–199 mg/dl (7.8–11.0
mmol/l)
Diabetes* 126 mg/dl ( 7.0 mmol/l) 200 mg/dl ( 11.1 mmol/l)

IFG (impaired fasting glycemia)

IGT (impaired glucose tolerance)

* A diagnosis of diabetes needs to be confirmed on a separate day.

 Prueba de
Promedio de
Hemoglobina Calificación
Glicemias
Glicosilada

5-6 % 80-120 mg/dl. Excelente

6-7 % 120-150 mg/dl. Muy Bueno

7-8 % 150-180 mg/dl. Bueno

8-9 % 180-210 mg/dl. Regular

9-10 % 210-240 mg/dl. Problemático

10-11 % 240-270 mg/dl. Malo

11-12 % 270-300 mg/dl. Muy Malo

 La HbA1c es mejor que la glucemia como factor
predictivo del riesgo de prediabetes
Veronica Hackethal, 02 de diciembre de 2016
La American Diabetes Association (ADA) recomienda
un límite de glucemia en ayunas de 100 a 125 mg/dl,
un límite de HbA1c de 5,7-6,4%, o un límite de
glucemia a las 2 horas de 140 a 199 mg/dl. La
Organización Mundial de la Salud (OMS) recomienda
el mismo límite de glucemia a las 2 horas que la ADA
pero aconseja un límite de glucemia en ayunas de
110 a 125 mg/dl, más alto, para indicar la
prediabetes. Por otra parte, el International Expert
Committee (IEC) recomienda un límite de HbA1c de
6-6,4% para identificar a las personas con riesgo
intermedio de diabetes.
http://espanol.medscape.com/verarticulo/5900992?nlid=110949_4103&src=WNL_esmdpls_161207_mscpedit_diab&uac=64285HX&impID=1248995&faf=1
 GLOSARIO
• Glucogénesis: vía de biosíntesis de glicógeno a partir
de glucosa.

• Glucógenolisis: vía de degradación del glicógeno a

glucosa.

• Glucólisis: ruta principal para la utilización de la

glucosa.

• Gluconeogénesis: todos los mecanismos y vías

responsables de convertir otras sustancias diferentes
de los CHO a glucosa o glicógeno.
 A: Pancreatic islet
surrounded by
exocrine tissue.
B: Confocal image
of an isolated
islet
immunolabelled for
insulin (red),
glucagon (green)
somatostatin
(blue).

C: Electron micrograph of a beta-cell showing some of

its 10,000 secretory granules. Insulin is stored in
the black crystals in the centres of the secretory
granules. D: Example of a granule captured just after
exocytosis before the insulin crystal has dissolved
 GLUCOSA

aa – aa - aa aa
GLUT4
ARNm
HK
GLUT4
G6P + Insulina

+ - +
Glucogenogenesis Glucólisis -
Gluconeogénesis
Glucógenolisis
+
+
Glucocorticoides
Adrenalina
Glycosylated (or glycated) hemoglobin
(hemoglobin A1c, Hb1c , or HbA1c, A1C) is a
form of hemoglobin used primarily to identify
the average plasma glucose concentration
over prolonged periods of time. It is formed in
a non-enzymatic pathway by hemoglobin's
normal exposure to high plasma levels of
glucose. Glycosylation of hemoglobin has
been implicated in nephropathy and
retinopathy in diabetes mellitus. Monitoring
the HbA1c in type-1 diabetic patients may
improve treatment.
Overview of mechanisms of current antihyperglycemic therapies for type 2 diabetes.
⊘ = Inhibition; ⊕ = Upregulation. AGI = alpha-glucosidase inhibitor; DPP-4 =
dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1; HGP = hepatic glucose
production; I/G = insulin:glucagon ratio; MET = metformin; SU = sulfonylurea; TZD =
thiazolidinedione.
 FARMACOS QUE
REGULAN LA GLICEMIA:

 NORMOGLICEMIANTES QUE
NO INDUCEN HIPOGLICEMIA

 NORMOGLICEMIANTES QUE
INDUCEN HIPOGLICEMIA
 BIGUANIDAS (METFORMINA)
• Mecanismo de Acción:
– Mejora la sensibilidad a la insulina por un mecanismo
postreceptor, incrementando la captación periférica de
glucosa, principalmente en miocitos y adipocitos
– Inhibe la gluconeogénesis y disminuye la liberación
hepática de glucosa al torrente sanguíneo
– Disminuye la absorción de glucosa en intestino
– Induce reducción de peso y mejora el perfil lipídico

• Tiene poco riesgo de producir hipoglucemias

 BIGUANIDAS (METFORMINA)
• Tiene buena absorción por vía oral, no se une a
proteínas plasmáticas, tiene una vida media de 3 horas
y se excreta por vía renal inalterada
• Efectos Adversos:
– El aumento de utilización de glucosa en eritrocitos y
enterocitos induce acumulación de ácido láctico, lo
cual es riesgoso en pacientes con nefropatías
severas, choque, insuficiencia respiratoria o cardíaca
– Anorexia, náuseas, disgeusia (mejoran al dar dosis
graduales y con los alimentos)
 BIGUANIDAS (METFORMINA)
• Precauciones y Contraindicaciones:
– No debe utilizarse en pacientes con alto riesgo de
acidosis láctica: insuficiencia renal, cardíaca o
respiratoria, ayuno prolongado, desnutrición,
deshidratación, alcoholismo, Cx mayores, choques
– No debe utilizarse en embarazo, lactancia ni en
diabéticos con predisposición a cetosis
– Debe suspenderse antes de la administración de
medios de contraste yodados (por dos días)
– Seguir periódicamente las concentraciones séricas de
ácido láctico en ancianos
 BIGUANIDAS (METFORMINA)
• Interacciones Medicamentosas:
– Puede interferir la absorción de la vitamina B12
• Usos terapéuticos:
– Diabetes Mellitus 2 con insulino resistencia
– Síndrome de ovario poliquístico
– Coadyuvante en el tratamiento de la obesidad
• Presentación:
tab 500, 850 y 1000 mg
 Metformin vs. Glipizide for Patients with Diabetes and Coronary Disease

Allan S. Brett, MD reviewing Hong J et al. Diabetes Care 2013 May.

Metformin was associated with better cardiovascular outcomes.

Observational data have suggested that metformin, compared with
sulfonylureas, protects patients with type 2 diabetes against adverse
cardiovascular events. In this double-blind trial from China, researchers randomly
assigned 304 diabetic patients with documented coronary artery disease to receive either
metformin or glipizide for 3 years. At baseline, mean glycosylated hemoglobin (HbA 1c) was
7.6%; most patients were taking aspirin and statins. During the study, insulin was added in
about 25% of patients in each group. After the formal 3-year randomized intervention,
monitoring of patients continued, with average total follow-up of 5 years.
The primary outcome was a broad composite of nonfatal cardiovascular
events and death from any cause. Sixty events occurred in 41 glipizide
recipients (35%), and 43 events occurred in 39 metformin recipients (25%).
In a time-to-event analysis, the primary outcome was less likely with
metformin than with glipizide (hazard ratio, 0.54; P=0.026). Fourteen
patients in the glipizide group and 7 in the metformin group died. Glycemic
control and lipid levels were similar in the two groups. On average, glipizide
recipients gained 1 kg, and metformin recipients lost 1 kg. The incidence of
hypoglycemia was similar in the two groups.
http://www.jwatch.org/na31389/2013/06/18/metformin-vs-glipizide-patients-with-diabetes-and-
 Medscape Medical News
Metformin and Insulin Combo Cuts Mortality in Type 2 Diabetes
Alexander M Castellino, PhD
May 16, 2016 1

• A new retrospective study indicates that, in type 2

diabetes, treatment with insulin is safer when it is
used together with metformin.
• In the research, recently published in PLoS One, a
team from Cardiff University, Wales, showed that
patients on insulin and metformin were at a
significant 40% reduced risk for death and a
significant 25% reduced risk for major adverse
cardiac events (MACE) compared with those
treated with only insulin
http://www.medscape.com/viewarticle/863314?
nlid=105309_3044&src=WNL_mdplsnews_160520_mscpedit_diab&uac=64285HX&spon=22&im
pID=1103526&faf=1
 Medscape Medical News
Metformin and Insulin Combo Cuts Mortality in Type 2 Diabetes
Alexander M Castellino, PhD
May 16, 2016 2

"If at all possible, patients with type 2 diabetes initiated on

insulin should also be given metformin," senior author Craig
Currie, PhD, professor of applied pharmacoepidemiology,
Cardiff University, Wales, told Medscape Medical News.

Asked to comment, Jason Baker, MD, assistant professor

in clinical medicine and attending endocrinologist at Weill
Cornell Medicine, New York, told Medscape Medical News:
"These results from a retrospective analysis are not
surprising and support what we already know. It is
reassuring and a reminder that insulin alone may not be
appropriate for some of our patients."
http://www.medscape.com/viewarticle/863314?
nlid=105309_3044&src=WNL_mdplsnews_160520_mscpedit_diab&uac=64285HX&s
 TIAZOLIDINEDIONAS

- Pioglitazona
– Rosiglitazona (retirada en Colombia, 2010. Falla cardíaca,
infarto de miocardio, eventos cerebrovasculares y muerte)
– Troglitazona ( retirada por hepatotoxicidad)
•Mecanismo de acción:
– Mejoran la respuesta de los tejidos blanco a
la insulina, por medio de la activación de
receptores nucleares, que promueven la
transcripción de genes que participan en el
metabolismo de la glucosa y de ácidos grasos
– Se disminuye la gluconeogénesis hepática
 TIAZOLIDINEDIONAS
• Buena absorción por vía oral, alta unión a proteínas y
metabolismo por CYP 450
• Efectos adversos:
– Hipoglucemia
– Aumento del volumen plasmático y edemas
– Anemia, cefalea, diarrea, dorsalgias
• Precauciones y contraindicaciones:
– Control periódico de las pruebas de función hepática
– Precaución en pacientes con insuficiencia cardíaca
Y antecedentes cardiovasculares
– No administrar en embarazo y lactancia
 TIAZOLIDINEDIONAS
• Interacciones medicamentosas:
– Hipoglucemia con otros hipoglucemiantes
• Usos:
– DM 2 con insulino resistencia
• Presentaciones:
– Pioglitazona: tab 30 mg
– Rosiglitazona: tab de 4 y 8 mg
 http://cme.medscape.com/viewarticle/724470?src=cmemp&uac=64285HX
From Heartwire CME
Another Leaked Rosiglitazone Manuscript?
Controversy Spikes as JAMA, Archives Publish New Papers CME
News Author: Shelley Wood / CME Author: Charles P. Vega, MD. Released: 07/01/2010;

• Graham et al's paper is a nationwide retrospective

analysis of 227 571 Medicare patients (mean age 74)
treated with either pioglitazone or rosiglitazone over a
three-year period, then followed for three years after
initiation of treatment. The investigators, from the FDA
and the Centers for Medicare & Medicaid Services
(CMS), found that after adjustment for potential
confounders, rosiglitazone was associated with a
significantly increased risk of stroke, heart failure, death,
and a composite of AMI, stroke, heart failure, or death,
as compared with pioglitazone. As previously reported,
only AMI was not significantly increased.
 Medscape Medical News from the: American Diabetes Association (ADA) 73rd
Scientific Sessions® , Heartwire > Conference News
CVD Reduced With Metformin, Higher With Rosiglitazone: Meta-Analysis
Michael O'Riordan Jun 24, 2013
CHICAGO, Illinois — The results of meta-
analysis presented this week at the
American Diabetes Association (ADA) 2013
Scientific Sessions adds new heft to earlier
observations that metformin is associated
with a reduction in the risk of cardiovascular
events while rosiglitazone (Avandia,
GlaxoSmithKline) increases the risk,
including the risk of heart failure and MI.
 INH. ALFA GLUCOSIDASA
• Medicamentos:
– Acarbosa y miglitol
• Mecanismo de acción:
– Inhiben las alfa- glucosidasas de las vellosidades
intestinales, bloqueando el desdoblamiento de los
polisacáridos a monosacáridos (formas absorbibles)
– No impiden la absorción de glucosa
• Tienen muy poca absorción sistémica (1-2%), y lo que
se absorbe se excreta inalterado por orina (t1/2=2 h), el
resto se excreta por heces
 INH. ALFA GLUCOSIDASA
• Efectos adversos:
– Alcanzan altas concentraciones en intestino grueso,
generando distensión abdominal, flatulencia y diarrea
– Aumento de transaminasas con dosis > 300mg/día
– Los EA pueden disminuirse con dosis graduales

• Precauciones y contraindicaciones:
– No administrar en casos de obstrucción intestinal,
procesos inflamatorios intestinales, síndromes de
mala absorción y en embarazadas
– Precaución en pacientes con hepato y nefropatías
 INH. ALFA GLUCOSIDASA
• Interacciones medicamentosas:
– Pueden interferir la absorción del hierro
– El efecto puede disminuirse por resinas de
intercambio iónico y antiácidos
– El miglitol puede disminuir la biodisponibilidad
de la ranitidina y del omeprazol
• Usos terapéuticos:
– Tratamiento coadyuvante en DM 2
 INH. ALFA GLUCOSIDASA
• Presentaciones:
–Acarbosa: tab de 50 y 100 mg
–Miglitol: tab de 50 mg
 INCRETINS

• The development of polypeptides in the

animal phyla include peptides, which
increase endogenous insulin -- referred to as
incretins.
• Exendin-4 is an incretin that is located in the
saliva of the Gila monster; it is also found in
humans in the L cell of the ileum as
glucagon-like polypeptide (GLP)-1 and
glucose-dependent insulinotropic polypeptide
in the K cells of the jejunum.
 INCRETINS
• The incretin hormones were discovered over 45 years after an enteral nutrition
administration was observed to provide a stronger insulin stimulus than one
obtained from an isoglycemic intravenous administration.[28] The incretins are
gut hormones triggered after ingestion of carbohydrates that cause an
increase in cyclic adenosine monophosphate and consequently release insulin.
Incretins are estimated to cause 70% of insulin secretion in healthy individuals.
[29]
However, this effect is impaired in patients with T2DM, possibly due to
decreased levels of glucagon-like-peptide-1(GLP-1), the most researched
incretin.[30,31] Additionally, incretins inhibit glucagon secretion, slow gastric
emptying, promote satiety, and likely improve pancreatic β-cell survival by
promoting resistance to apoptosis.[32] The mechanism works in a glucose-
dependent fashion; therefore, agents utilizing this mechanism do not typically
cause hypoglycemia. GLP-1 has a half-life of less than four minutes due to
rapid degradation by the enzyme dipeptidyl-peptidase IV (DPP-IV).[33,34] New
pharmacologic treatments for T2DM have focused on GLP-1 receptor (GLP-
1R) agonists and DPP-IV enzyme inhibition; Table summarizes their key
information.

• http://www.medscape.com/viewarticle/743328_5
 Incretin-Based Therapies for T2DM
• Two new classes of drugs for the treatment of type
2 diabetes mellitus (T2DM) utilize the known
actions of glucagon-like peptide (GLP)-1 in
regulating both alpha and beta cells of the pancreas
to produce glucose-lowering effects.
• The GLP-1 receptor agonists (exenatide and
liraglutide, sc) and dipeptidyl peptidase (DPP)-4
inhibitors (sitagliptin, vildagliptin, and saxagliptin:
oral) are collectively referred to as "incretin
therapies“, and exert their glucoregulatory effects
by stimulating insulin secretion from beta cells and
inhibiting glucagon release from alpha cells in a
glucose-dependent fashion.
 INCRETINS
• Therapy for type 2 diabetes mellitus (T2DM) has
developed into the use of incretins to lower
blood glucose. Additionally, several other
pleiotropic effects are being identified and are in
development.
• As such, incretin-based therapies continue to be
an evolving field in the treatment of T2DM.
• A significant number of patients with T2DM have
been exposed to GLP-1 receptor agonist-based
therapy.
 INCRETINS
• There is an accumulating body of information
evaluating cardiovascular surrogate markers
and event rates with the use of incretin-based
therapies, including exenatide and other GLP-1
agents, which are in various stages of
development.

• Some of these studies have compared GLP-1

receptor agonist surrogate markers with insulin,
dipeptidyl peptidase (DPP)-4 inhibitors, and
other oral antidiabetic agents.
 INCRETINS
• Because GLP-1 receptor agonists and DPP-4
inhibitors address different pathophysiologic
pathways in the GLP-1 system, they have
significant advantages and disadvantages that
need to be considered when individualizing
treatment.
• Compared with other diabetes medications,
GLP-1 receptor agonists and DPP-4 inhibitors
offer the benefit of a low incidence of
hypoglycemia. In addition, DPP-4 inhibitors are
generally weight neutral, whereas GLP-1
receptor agonists promote weight loss.
 INCRETINS
• Liraglutide is an analog of human GLP-1R agonist with an amino acid
substitution and an acylated side chain which help shield liraglutide from
degradation by DPP-IV, increasing its half-life to approximately 13 hours.
Six randomized phase-III clinical trials, Liraglutide Effect and Action in
Diabetes (LEAD), revealed liraglutide's improved glycemic control in adults
with T2DM compared to rosiglitazone, glimepiride, placebo, insulin glargine,
and exenatide. Consequently, the FDA approved liraglutide as an adjunct to
diet and exercise to improve glycemic control in adults with T2DM. The
LEAD-3-Mono showed greater A1c improvement with liraglutide 1.2 mg
(−0.84%) and 1.8 mg (−1.1%) compared to glimepiride (−0.51%, P = 0.0014
and P < 0.0001 respectively) as monotherapy. LEAD 5 showed a greater
improvement in A1C with liraglutide 1.8 mg (−1.33%) compared to insulin
glargine (−1.09%, P = < 0.0001), titrated using a dosing algorithm, in
combination with metformin and a sulfonylurea. The LEAD-6 trial resulted in
improved A1c with liraglutide 1.8 mg (−1.12%) compared to exenatide
(−0.79%, P < 0.0001) in combination with metformin or a sulfonylurea.

http://www.medscape.com/viewarticle/743328_5
 INCRETINS
http://www.medscape.com/viewarticle/743328_5
• Transient nausea and vomiting are prominent with GLP-1R
agonists; however, titration decreases these effects. Studies in
mice have linked liraglutide to increased risk of thyroid C-cell
focal hyperplasia and C-cell tumors. The liraglutide drug levels
used in mice were much higher than the levels expected in
humans with recommended doses. The FDA has concluded
that the carcinoma risk is low to humans. Pancreatitis has
been linked to medications altering the GLP-1 pathway,
including GLP-1R agonist and DPP-IV inhibitors. Patients with
diabetes have a higher baseline risk of pancreatitis and the
post-marketing data have lacked some data showing
causality; therefore, the FDA has not yet established an
increased risk. The FDA has required additional studies further
analyzing thyroid C-cell tumors and pancreatitis.
 FDA Warns of Serious Risks Associated With Liraglutide

06/13/2011
http://www.medscape.com/viewarticle/744477?src=mp&spon=22

• Liraglutide causes dose-dependent and treatment-

duration-dependent thyroid C-cell tumors at clinically
relevant exposures in both sexes of rats and mice,
according to an alert sent today from MedWatch, the
FDA's safety information and adverse event reporting
system. It is unknown whether liraglutide causes thyroid
C-cell tumors, including medullary thyroid carcinoma, in
humans, as human relevance could not be ruled out by
clinical or nonclinical studies. In addition, in clinical trials
studying liraglutide, there were more cases of
pancreatitis in patients treated with liraglutide than in
patients treated with comparable medications
 INCRETINS

• Saxagliptin is an oral DPP-IV inhibitor indicated as an

adjunct to diet and exercise to improve glycemic control
in adults with T2DM. Inhibition of the DPP-IV enzyme
potentiates GLP-1 resulting in incretin-like actions with
the exception of slowed gastric emptying. DPP-IV
inhibitors have not been linked to weight loss.
Rosenstock et al compared saxagliptin 2.5 mg, 5 mg, and
10 mg as monotherapy to placebo, resulting in A1c
reductions of −0.43%, −0.46%, and −0.54%, respectively,
compared to placebo (0.19%, P < 0.0001 for all).
Saxagliptin has also shown A1c improvements as an
adjunct to metformin, thiazolidinediones, and glyburide.
http://www.medscape.com/viewarticle/743328_5
 FDA Studying Whether Certain Diabetes Drugs Pose Pre-Cancer Risk
http://es-mg42.mail.yahoo.com/neo/launch?.rand=b1jin8uj0tkks#article1
By Kelly Young

• The FDA is investigating whether diabetes drugs in the class known as

incretin mimetics pose an increased risk for pancreatic duct
metaplasia.
• The agency is looking at unpublished data on pancreatic toxicity in a
small number of tissue samples taken from patients with diabetes who
died. It will examine the researchers' methodology and the samples
firsthand before concluding whether there is a risk to patients.
• Incretin mimetics include exenatide (Byetta, Bydureon), liraglutide
(Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync),
saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano,
Oseni), and linagliptin (Tradjenta, Jentadueto). The drugs' labels
already carry warnings about the risk for pancreatitis.
• Healthcare providers may continue prescribing the drugs according to
the labels and should report adverse events to the FDA.
 Sitagliptin Seems as Safe as Other Diabetes Drugs
By Amy Orciari Herman
http://es-mg42.mail.yahoo.com/neo/launch?.rand=avgiu8cpdoo75#article1

• The dipeptidyl peptidase-4 inhibitor sitagliptin, approved to treat type 2

diabetes in 2006, appears to be as safe as other diabetes drugs,
according to a retrospective cohort study in BMJ.
• Using a large U.S. database, researchers studied nearly 73,000 adults
who began oral medications for diabetes from 2004 through 2009;
about 10% used sitagliptin, usually in combination with other drugs.
• During a mean follow-up of 2.5 years, all-cause hospital admission or
death occurred in 20% of all patients. After multivariable adjustment,
risk was similar in sitagliptin users and nonusers, even in analyses
limited to those with ischemic heart disease or reduced kidney
function. In addition, the authors write, there were "no safety 'signals'
related to cardiovascular related hospital admissions or death,
supporting the premise that sitagliptin seems to be safe in patients
with diabetes."
• BMJ article (http://www.bmj.com/content/346/bmj.f2267)
 The Fundamental Role of Dipeptidyl Peptidase-4
Inhibitors and Glucagon-like Peptide-1 Receptor
Agonists in Clinical Practice .
Guillermo E. Umpierrez, MD, Luigi Meneghini, MD
Endocr Pract. 2013;19(4):718-728.

Conclusion: Incretin-based therapies are

characterized by an overall favorable safety profile
and weight effect, a low risk of hypoglycemia, and
clinically meaningful improvements in HbA1c. Based
on an expanding and favorable literature describing
their use in various patient populations, the guidelines
of the American Association of Clinical
Endocrinologists and the recently updated guidelines
from the American Diabetes Association assign these
agents a central role in the treatment of T2D.
 INHIBIDORES DE
SGLT2 (sodium/glucose cotransporter 2 )

SANGRE
 CANAGLIFLOZINA
Se usa junto con dieta y ejercicio, y algunas veces
con otros medicamentos, para reducir los niveles de
azúcar en sangre en pacientes con diabetes tipo 2.

La canagliflozina pertenece a una clase de

medicamentos llamados inhibidores del
co-transportador 2 de sodio-glucosa
(SGLT2). Reduce la glicemia al hacer que la
nefrona elimine más glucosa en la orina.
La canagliflozina no se utiliza para tratar la diabetes
tipo 1 .
 INHIBIDORES DE
SGLT2 (sodium/glucose cotransporter 2 )
En el estudio de seguridad cardiovascular de
canaglifozina para pacientes con diabetes de tipo 2
(CANVAS), individuos con diabetes de tipo 2 con
alto riesgo cardiovascular tratados con
canaglifozina presentaron una reducción
significativa de muertes por causa cardiovascular,
infarto agudo al miocardio no fatal y evento vascular
cerebral isquémico no fatal en relación al placebo.
Estos resultados fueron similares a lo obtenido en el
estudio EMPA-REG con empaglifozina, sugiriendo
un efecto de clase benéfico para pacientes con
diabetes de tipo 2 y alto riesgo cardiovascular.
 INHIBIDORES DE SGLT2
Aunado a ello, un nuevo reporte publicado en Lancet Diabetes and
Endocrinology basado en el sistema de farmacovigilancia de la FDA
(FAERS), mostró que de los eventos de amputaciones en pacientes
tratados con inhibidores de SGLT2, en el 86% (57 de 66 eventos
reportados) de ellos se colocaba a la canaglifozina como
medicamento sospechoso o concomitante. De los eventos notificados,
36% de los casos presentaban alguna característica sugestiva de pie
diabético. En este último trabajo se calculó que la frecuencia de los
reportes de amputaciones con canaglifozina como sospechoso o
concomitante era de 3,4 eventos por 1000 reportes (IC 95%: 2,6 –
2,46). Asimismo, tratando de detectar señales de eventos adversos, se
comparó la relación de amputaciones con canaglifozina,
dapaglifozina y empaglifozina en relación a otros hipoglucemiantes
orales para diabetes de tipo 2 y se encontró que también canaglifozina
presentaba mayor relación proporcional de reporte que dapaglifozina y
empaglifozina (5,33 frente a 0,25 frente a 2,37).
NORMOGLICEMIANTES
(QUE INDUCEN HIPOGLICEMIA)
 SULFONILUREAS
• Mecanismo de acción:
– Estimulan la liberación de insulina desde las
células beta pancreáticas al bloquear canales de
potasio
– Disminuyen la secreción de glucagón
– Mejoran la actividad periférica de la insulina
• No son efectivas en pacientes cuyo páncreas
endocrino no puede producir insulina
• Tienen buena absorción por vía oral y se
metabolizan en hígado y riñón
 SULFONILUREAS
• Se unen a proteínas en forma importante lo que
genera algunas interacciones medicamentosas
• La clorpropamida tiene el tiempo de vida media
más prolongado (36 horas), por lo cual requiere
un manejo muy cuidadoso
• La tolbutamida tiene la t1/2 más corta (6 horas)
• La glibenclamida y la gliclazida tienen vida
media intermedia (10 horas)
• La glibenclamida se concentra en células beta.
 SULFONILUREAS
• Efectos adversos:
– Hipoglucemia, trastornos gastrointestinales, rash,
urticaria, discrasias sanguíneas (agranulocitosis)
– Hiponatremia por clorpropamida en ancianos
• Precauciones y Contraindicaciones:
– No deben administrase en embarazadas, ya que
pueden cruzar la placenta y ejercer efectos fetales
– Tampoco en pacientes bajo situaciones de estrés
médico-quirúrgico (cirugías, traumas, UCI, etc)
– Mayor susceptibilidad a hipoglucemias en
ancianos, pacientes con nefro o hepatopatías,
desnutrición
 SULFONILUREAS
• Interacciones Medicamentosas:
– Hay hipersensibilidad cruzada con otras sulfas como
las sulfonamidas, furosemida, celecoxib
– La clorpropamida genera efecto antabuse (disulfiram)
– Con anticoagulantes puede potenciarse el efecto
hipoglucemiante y aumentar el riesgo de sangrados
– Las sulfas y el clofibrato potencian la hipoglucemia

• Usos Terapéuticos:
– DM 2 insulino deficientes, que no se han controlado
con dieta y ejercicio. Deben iniciarse gradualmente
 SULFONILUREAS
• Presentaciones:
– Glibenclamida tab 5 mg
– Gliclazida: tab 80 mg
– Glimepirida: tab 2 y 4 mg
 MEGLITINIDAS
(REPAGLINIDA – NATEGLINIDA)
• Mecanismo de Acción:
– Similar al de las sulfonilúreas, con un inicio más
rápido y proporcional a los niveles de glucosa (debe
administrarse antes de las comidas principales)
• Tienen buena absorción por vía oral, amplia unión a
proteínas y se metabolizan por el sistema CYP 3A4 con
excreción biliar para la repaglinida y renal para la
nateglinida
• El tiempo de vida media de la repaglinida es de una hora
y el de la nateglinida, de 1,5 horas
 MEGLITINIDAS
(REPAGLINIDA – NATEGLINIDA)
• Efectos adversos:
– Hipoglucemia
– Con repaglinida infecciones respiratorias y raramente
alergias, cefalea, náuseas, constipación, leucopenia,
trombocitopenia, arrítmias, parestesias
– Con nateglinida: elevación transitoria de enzimas
hepáticas, hipersensibilidad y síntomas de TGI
• Precauciones y contraindicaciones:
– No administrar en embarazo y lactancia, DM 1,
insuficiencia hepática, medicamentos que interfieran
con CYP 3A4
 MEGLITINIDAS
(REPAGLINIDA – NATEGLINIDA)
• Interacciones farmacológicas:
– Similares a los otros hipoglucemiantes
• Usos terapéuticos:
– Coadyuvantes en el tratamiento de DM 2
• Presentaciones:
– Repaglinida: tab 1 y 2 mg
– Nateglinida: tab 60 y 120 mg
INSULINAS
 SÍNTESIS Y SECRECIÓN
• Islotes pancreáticos

• Células beta

• Preproinsulina Proinsulina Insulina

• Si la secreción es desencadenada por la glucosa se requiere

que esta entre a la célula beta y se metabolice, además se
dice que esta es bifásica

• La sangre arterial en el islote de langerhans fluye desde las

células beta hacia las alfas y las deltas.
 RECEPTOR
• El receptor insulínico es una combinación de cuatro
subunidades enlazadas a través de puentes
disulfuro.

• 2 subunidades alfa -fuera de la membrana celular

• Dos beta -atraviesan la membrana y sobresalen en

el interior del citoplasma.

• La insulina se une a la subunidad alfa

ACCIONES DE LA
INSULINA
 METABOLISMO
HIDROCARBONADO
• Transporte de glucosa al interior de las célula
(hígado, músculo y adiposito).
• Incremento de transportadores específicos de
glucosa y exosas.
• Estimula las enzimas participantes en la
glucogenogénesis y glucólisis. (músculo)
• Inhibe mecanismos enzimáticos responsables de la
gluconeogénesis y glucogenolisis, reduciendo la
liberación de glucosa (hígado).
• Efecto neto de disminución de la glucemia.
• Efecto neto de disminución de la glucosuria.
METABOLISMO PROTEICO Y
MINERAL
• Estimula el transporte activo de aminoácidos a través de las
membranas celulares.

• Promueve la captación de aminoácidos y la síntesis proteica e

inhibe su degradación metabólica. (músculo)

• Favorece el ingreso de potasio a las células (estímulo de la

Na+K+ ATPasa)

• Inhibe la salida de calcio de las células.

• Aumento intracelular de magnesio y fosfatos inorgánicos.

• Estimulan la síntesis de DNA y RNA.

METABOLISMO LIPÍDICO
• Inhibe la lipasa específica que interviene la movilización de los
ácidos grasos, al reducir la concentración intracelular de AMPc.
(adiposito)

• Disminuye rápidamente la hiperlipemia de los estados diabéticos

y la producción de cuerpos cetónicos en el hígado.

• Antagóniza la acción lipolítica de catecolaminas, cortisol y

hormona del crecimiento, deprimiendo la liberación de glicerol y
ácidos grasos libres.

• Deprime la secreción de VLDL e impide su organización y

ensamblaje.
 TRATAMIENTO CON INSULINA.
PREPARADOS
 Actualmente se dispone en el mercado de una gran
variedad de insulinas

 Todas ellas tienen en común haber sido obtenidas

por tecnología ADN recombinante

 Presentan una concentración de 100 unidades/ml.

(unitage)

 Presentan diferencias en su farmacocinética, modo

de administración
 INSULIN DEGLUDEC: is a modified human insulin in which a single amino acid
is deleted and a conjugated hexadecanedioic acid is added via a gamma-L-
glutamyl spacer at the amino acid lysine, at position B29.
The hexadecanedioic acid allows the formation of multihexamers in subcutaneous
(SC) tissues following administration, creating an SC depot that results in slow
insulin release to the systemic circulation.

Also, insulin degludec is bound by plasma albumin, further extending its duration.
Therefore, insulin degludec has a slow onset of action (30–90 minutes)—similar to
that of insulin glargine and detemir—and no peak in activity because of the slow
diffusion to the systemic circulation. The duration of action of insulin degludec is
reported to be as high as 42 hours, compared with 18 to 26 hours provided by other
long-acting insulins (glargine and detemir), making it a once-daily basal insulin.
 HUMULIN® R / HUMULIN® N /
HUMULIN® 70/30
Cada ml de HUMULIN® R contiene insulina
humana regular 100 U.I

Cada ml de HUMULIN® N contiene insulina

humana NPH en suspensión isofánica, 100
U.I

Cada ml de HUMULIN® 70/30 contiene

insulina humana NPH en suspensión
isofánica 70 U.I., insulina humana regular 30
U.I
Insulinas: Presentaciones en
Colombia

Amelia Meza Acevedo

V SEMESTRE
HUMALOG®:100 UI/mL
 • Nombre genérico : Insulina lispro

• Humalog KwikPen 100 unidades/ml, solución inyectable

• Descripción general
• Humalog es una solución estéril, transparente, incolora y acuosa.
• Humalog KwikPen 100 unidades/ml, solución inyectable: Cada envase contiene 3
ml equivalentes a 300 unidades de insulina lispro.

• Indicaciones terapéuticas
• Para el tratamiento de adultos y niños con diabetes mellitus que requieren insulina
para el mantenimiento de la homeostasia normal de la glucosa. Humalog
también está indicado en la estabilización inicial de la diabetes mellitus.
•
• Humalog puede ser administrado poco antes de las comidas. Cuando sea
necesario Humalog puede ser administrado poco después de las comidas. Los
preparados de Humalog deben ser administrados por inyección subcutánea o por
bomba de perfusión subcutánea continua

• Contraindicaciones
• Hipersensibilidad a insulina lispro o a alguno de los excipientes. Hipoglucemia
NOVORAPID®:100 UI/mL
 • Nombre genérico : Insulina aspartato
• Nombre del medicamento: NovoRapid FlexPen 100 unidades/ml solución
inyectable en pluma precargada.

• Composición cualitativa y cuantitativa:1 ml de solución contiene 100 unidades

de insulina aspart* (equivalente a 3,5 mg). 1 pluma precargada contiene 3 ml
equivalentes a 300 unidades.

• Forma farmacéutica: Solución inyectable.

• La solución es transparente, incolora y acuosa.

• Indicaciones terapéuticas:
• NovoRapid está indicado para el tratamiento de diabetes mellitus en adultos,
adolescentes y niños de 2 años en adelante.

• Posología y forma de administración:

• Según las necesidades del paciente.NovoRapid FlexTouch es una pluma
precargada (con un código de colores) diseñada para ser utilizada con las agujas
desechables NovoFine o NovoTwist de hasta 8 mm de longitud. Con FlexPen
es posible seleccionar dosis de 1 a 60 unidades en incrementos.

perfusión subcutánea continua de insulina (PSCI) en bombas de perfusión.

vía intravenosa (por médicos u otros profesionales sanitarios)
APIDRA®: 100 UI/mL
• Nombre genérico :Insulina glulisina.

• Presentaciones: Lapicera prellenada descartable

SoloSTAR con 3 ml: estuche con 1 lapicera
• .
• indicaciones: Tratamiento de la diabetes mellitus en
pacientes adultos, adolescentes y niños a partir de
los 6 años, cuando se requiera tratamiento con
insulina.

• Posología: juicio medico.

• Contraindicaciones y advertencia : Pacientes con
hipersensibilidad conocida a insulina glulisina o a
cualquiera de los excipientes. Hipoglicemia
• NO administras vía IV, no mezclar con otras
NOVOLIN R®: 100 UI/mL
 • Nombre genérico: Insulina humana regular.
• 1ml de solución contine 100UI de insulina
humana cloruro de
zinc,glicerol,metracresol,hidroxido de sodio,
acido clorhídrico, y agua para inyectables
• Precauciones : mantener fuera del alcance de
los niños, no congelas, mantener vial en caja
para protegerlo de la luz después de abrirlo.
• Vía de administración : subcutánea e
intravenosa
INSULEX N ®: 100 UI/ml
 Nombre genérico : Insulina isófana
Presentación : 100 U/ml suspensión
inyectable
caja con un frasco ámpula con de 10 ml.
Turbio ,blanquecino,
Administración: Subcutáneo -
intramuscular
Contraindicaciones: Hipersensibilidad,
hipoglucemia, vía IV
LANTUS®: 100 UI/mL
 • Nombre genérico: Insulina glargina
• Cada ml de solución inyectable en frasco-ampolla contiene:
Insulina Glargina: 3.6378 mg (equivalentes a 100 U de
Insulina Recombinante Humana)
• Lápices aplicadores desechables prellenados :
(Solostar):10.9134mg de insuli na glargina equivale a
300 U de insuliana humana
• Indicaciones: Tratamiento de pacientes adultos y
pediátricos con diabetes mellitus tipo 1,
• Posología y administración : Se administra vía
subcutánea 1 vez al día. Puede ser administrada a
cualquier hora del día, sin embargo siempre a la misma
hora.
LEVEMIR®: 100 UI/mL

Nombre genérico: Insulina detemir

Levemir 100 U/ml solución inyectable en
pluma precargada
Indicaciones; se utiliza para reducir los
niveles altos de azúcar en sangre en
adultos, adolescentes y niños de 2
años en adelante con diabetes.
Administración : Subcutánea
 GLP-1 Agonist + Long-Acting
Insulin
• lixisenatide/insulin glargine
• subcutaneous injection
• (33mcg/100units) per mL
• Available as a 3-mL single-use pen Starting dose
• Patients inadequately controlled on <30 units of basal insulin: 30
units (ie, 30 units insulin glargine/10 mcg lixisenatide) SC qDay
• Patients inadequately controlled on 30-60 units of basal insulin or on
lixisenatide: 15 units (ie, 15 units insulin glargine/5 mcg lixisenatide)
SC qDay
• Maximum daily dose: 60 units (ie, 60 units insulin glargine20 mcg
lixisenatide
• Administer within the hour prior to the first meal of the day
• Use alternative antidiabetic products if daily dosage is <15 units or
>60 units
• The pen delivers doses from 15 to 60 units with each injection
 GLP-1 Agonist + Long-Acting
Insulin
liraglutide/insulin degludec
•subcutaneous injection,3.6mg/100units per mL
•Available as a 3-ml single-use pen Recommended starting dose:
16 units (ie, 16 units insulin degludec and 0.58 mg liraglutide) SC
qDay
•Maximum daily dose: 50 units (50 units of insulin degludec and
1.8 mg of liraglutide)
•The pen delivers doses from 10-50 units with each injection
•Each dosage unit contains 1 unit of insulin degludec and 0.036
mg of liraglutide
•Use alternative antidiabetic products if patients require a daily
dosage persistently below 16 units or over 50 units
 FARMACOCINÉTICA
• La insulina solo puede administrarse por vía
parenteral (s.c. o i.v.)

• La insulina circula en plasma enlazada a

betaglobulinas.

• La absorción es más rápida y completa si la

inyección de insulina se ejecuta en el tejido
celular subcutáneo de la piel del abdomen,
que en otras regiones.
• El volumen de distribución se aproxima al
volumen de líquido extracelular.

• La vida media de la insulina, proinsulina y

peptido C es diferente.

• La insulina se puede degradar en el hígado,

músculo y riñones.

• La enzima metabolizadora es la glutation-

insulina-transhidrogenasa que produce la
inactivación de la insulina.
 PAUTAS EN EL TRATAMIENTO
PROLONGADO
• La dosis media que requiere un paciente diabético es de 0.2 a 1
U/Kg/día

• Al comienzo una dosis diaria de 0.2 – 0.3 U/Kg/día para los

diabéticos de tipo 2, y una dosis total diaria de 0.4 – 0.6
U/Kg/día para los diabéticos de tipo 1.

• Existen dos modalidades en la administración del tratamiento

prolongado:

1. Pauta convencional.

-En una sola dosis de acción de insulina intermedia.

-En dos dosis, una matutina y otra por la tarde o por la noche de
insulina.
2. Pauta intensiva.

Dirigida principalmente a pacientes con diabetes mellitas tipo 1 .

• Múltiples dosis de insulina

• Equilibrio cuidadoso entre ingestión de alimentos, actividad fisica y dosis de

insulina

• Autocontroles diarios de glucemia capilar

• Plan de autoajuste de la dosis de insulina

• Definir niveles de glucemia optimos para cada paciente

• Visitas frecuentes al equipo de seguimiento

• Educación y motivación del paciente y del equipo que le atiende

• Apoyo psicologico

• Determinación trimestral de la hemoglobina glucosilada (HbA1c)

EFECTOS ADVERSOS
DE LA INSULINA
 1. HIPOGLUCEMIA

Es el efecto adverso más frecuente. Todo

paciente que esté bajo terapéutica con
insulina debe llevar una tarjeta o
medalla que contenga la información de
su tratamiento con insulina.

El 5% de las muertes de los diabéticos

puede ser atribuido a hipoglucemia.
 PRINCIPALES CAUSAS DE
HIPOGLUCEMIA SON:

• Ejercicios físicos excesivos e intensos.

• Omisiones en las comidas, ayuno.
• Dosis excesivas de insulina.
• procesos de absorción
• Ser adulto mayor.
 SIGNOS COMUNES DE
HIPOGLICEMIA:
– Sensacion Hambre
– Nauseas
– Debilidad,
– Sudoración,
– Taquicardia,
– Visión borrosa,
– Cefaleas y temblores.
– Confusión e incoherencia,
– Convulsiones
– Pérdida del conocimiento,
– Shock hipoglicémico y coma.
 2. INMUNES

Alergias locales se presentan en el 20%

de los pacientes que reciben insulina.

También se puede presentar

inmunorresistencia por presencia de
títulos bajos de IgG.
Las reacciones alérgicas
consisten en:
– Prurito.
– Enrojecimiento.
– Tumefacción ligera.
– Calor y dolor en el lugar de la
inyección.
– Urticarias generalizadas, edema
angioneurótico y reacción anafiláctica
en 1 % de los casos.
3. TRASTORNOS LOCALES

“Las inyecciones subcutáneas repetidas de

insulina en el mismo lugar, pueden
producir reacciones en el tejido celular
subcutáneo.”
Insulin or Sulfonylureas to Supplement Metformin in Patients with Diabetes?

Thomas L. Schwenk, MD reviewing Roumie CL et al. JAMA 2014 Jun 11.

Insulin plus metformin was associated with higher all-cause mortality in

a retrospective study.
Metformin and lifestyle modifications are the mainstay of initial
treatment for patients with type 2 diabetes. The choice of a second
medication for patients who do not achieve full control with this
regimen is unclear. Investigators conducted a retrospective cohort study in the Veterans
Affairs healthcare system and identified patients who had initiated metformin and then received
either insulin or a sulfonylurea to achieve better glycemic control between 2001 and 2008. About
12,000 sulfonylurea recipients and about 2500 insulin recipients were matched closely for many
demographic and clinical covariates through propensity scores. Median age was 60, and median
glycosylated hemoglobin (HbA1c) level was 8.1% in both groups.
The combined endpoint of acute myocardial infarction and stroke
occurred in a similar proportion of each group (10.2 per 1000
person-years for insulin vs. 11.9 per 1000 person-years for
sulfonylureas), but all-cause mortality through 2009 was 44% more
common in those receiving insulin — a significant difference .
http://www.jwatch.org/na34894/2014/06/10/insulin-or-sulfonylureas-supplement-metformin-patients?query=etoc_jwgenmed
 Diabetic Ketoacidosis
• Is a potentially fatal acute metabolic complication of
diabetes mellitus. It is characterized by the biochemical
triad of hyperglycemia, ketonemia, and metabolic
acidosis.

• It is typically associated with type 1 diabetes but may

also occur in type 2 diabetes during periods of infection,
trauma, cardiovascular injury, or other emergencies. It is
more common in young people with type 1 diabetes and
in females. It may be the presenting manifestation of
diabetes. It can be precipitated by many clinical
situations. The most common include inadequate dosing
of insulin and infection, pancreatitis, cardiovascular
disorders (myocardial infarction, stroke), and drug use
(steroids, antipsychotics )
 Diabetic Ketoacidosis
Results from severe alterations in carbohydrate, protein, and lipid
metabolism. In simple terms, it is the consequence of severe cell
starvation and death resulting from a relative or complete deficiency of
insulin needed to transport glucose into the cells.

Increased gluconeogenesis, increased glycogenolysis, and decreased

use of glucose by the muscles, liver, and fat lead to profound metabolic
derangements. Insulin deficiency promotes lipolysis. Lipolysis also
plays a key role in promoting metabolic decompensation by providing
the substrate for the formation of ketone bodies (acetone, beta-
hydroxybutyric acid, and acetoacetic acid).

Decreased clearance of ketone bodies leads to ketonemia and results

in an anion gap metabolic acidosis. There are also elevated levels of
proinflammatory cytokines and procoagulant factors (C-reactive protein
and interleukin-6 and -8) that predispose the patient to thrombosis.
 • CLINICAL MANIFESTATION AND
DIAGNOSIS
Severe disease can develop in less than 24
hours after the onset of ketosis. Clinical
manifestations include polyuria, polydipsia,
polyphagia, and weakness.
Glucosuria can lead to profound intravascular
volume depletion, manifested by dry mucous
membranes, flattened neck veins, tachycardia,
hypotension, and orthostasis. Nausea and
vomiting are common, occurring in up to 80%
of patients.
 Abdominal pain occurs in 30% of individuals. Patients often
have a fruity odor to their breath, resulting from elevated
serum acetone. Tachypnea is common and can contribute
to the intravascular volume depletion.
It occurs as a compensatory response to the underlying
metabolic acidosis seen in this disorder. In severe cases
patients may exhibit Kussmaul respirations (rhythmic,
gasping deep respirations with normal or reduced
frequency).
Infection and sepsis are commonly associated precipitating
factors and can further contribute to volume depletion. In
short, DKA is nearly universally associated with profound
intravascular volume depletion and restoration of this is a
cornerstone of therapy. Depending on the severity of the
metabolic derangement, patients may have altered mental
status. The spectrum can vary from mild confusion to coma.
• DIABETIC KETOACIDOSIS TREATMENT
focuses on normalization of the serum glucose and
electrolytes, restoration of the intravascular volume, and
resolution of the metabolic acidosis.

Hyperglycemia should be initially treated with a

continuous infusion of intravenous insulin. An initial
intravenous bolus of regular insulin at 0.1 U/kg body
weight, followed by a continuous infusion of regular
insulin at a dose of 0.1 U/kg/hour is the standard therapy.
Long-acting and oral preparations should be strictly
avoided during the initial treatment of this disorder as
rapid fluctuations in serum glucose levels may be
experienced and are more easily managed with regular
insulin
 Esquema móvil de Insulina
( Subcutánea )
Glucosa mg /dL

101-150 ............. 3-5 U

151-200 ............. 6-10
201-250 ............. 9-15
251-300 ............. 12-20
> 301 ............. 15-25
Mabel Valsecia
Farmacología Medicina
The treatment of DKA focuses on the restoration of the intravascular volume,
normalization of serum glucose and electrolytes, and resolution of the
metabolic acidosis. Hyperglycemia should be initially treated with an initial
intravenous bolus of regular insulin at 0.1 U / kg body weight, followed
by a continuous infusion of regular insulin at a dose of 0.1 U/kg/hour .
Solution of insulin 50 U in 500 mL saline solution have to be prepared
for continuous infusion. DE ACUERDO AL TEXTO ANTERIOR SI EL
PACIENTE PESA 95 KILOS, CALCULAR :

•LA DOSIS DE INICIO

•LA DOSIS DE INFUSION CONTINUA
•EXPLICAR LA PREPARACION DE LA SOLUCION
•VOLUMEN DE LA SOLUCION QUE CONTIENE LA DOSIS CALCULADA
PARA INFUSION
•VELOCIDAD DE INFUSION EN BOMBA PERISTALTICA ml / mint,
PARA CUMPLR LA ORDEN.
http://boards.medscape.com/forums?128@672.C07ua0Jb3QR@.2a0b59bb!comment=1

Friday, September 16, 2016

 Adding basal insulin plus at least one meal
time insulin is better than twice a day pre-
mixed insulin. 1
Patients failing oral therapy often require step up to basal insulin. If
that doesn't do the trick, the choice seems to be either basal bolus
therapy or split mixed (70/30) twice daily. The former is likely more
effective but requires more injections. The later is more convenient but
probably not as good. The study "Comparison of 3 intensified insulin
regimens added to oral therapy for type 2 diabetes: Twice-daily aspart
premixed vs glargine plus 1 prandial glulisine or stepwise addition of
glulisine to glargine" presented at the ADA and reported by it's sponsor
Sanofi showed that when compared with premixed insulin dosing,
glargine plus meal time insulin got more patients to HbA1c goal with
little hypoglycemic (14% vs. 24%) which shouldn't come as a surprise.
However, there wasn't much difference between adding 3 doses of meal
time insulin vs. one (largest meal). Thus, when diabetics do not achieve
goal on basal insulin, adding one dose of prandial insulin to the largest
meal seems like a very reasonable step before going to basal bolus
therapy.
 Metformin more cost effective than diet and excercise
for diabetes prevention. 2
These were the results of an analyses of 10-year data from the
Diabetes Prevention Program (DPP) The original 3 year DPP study
showed that lifestyle modification reduced the likelihood of
developing diabetes by 58% compared to just 31% with Metformin,
and after 10 years total, diet and exercise was associated with an
overall 31% reduction of developing diabetes, compared to metformin
which reduced the risk by 19%. The 10-year costs of lifestyle
intervention was about $4,500, metformin $2,000, and doing nothing
$750. When costs of the intervention were added to dollars saved
from not developing diabetes, the total return on investment showed
that the lifestyle program cost $1,500 per person while metformin
saved $30 per person over 10 years. In other words, though diet and
exercise did better in preventing diabetes than metformin, it actually
costs more than it saved. Metformin seems to be a more cost-effective
preventative strategy for type 2 diabetes (based on these findings)
then diet and exercise.
LIRAGLUTIDE leads to weight loss in non-diabetics, and
more effective when used earlier in those with diabetes. 3
Novo Nordisk, the makers of liraglutide , had a very good ADA 2011. Two
studies seemed particularly important. The first analysis looked at the
efficacy of using liraglutide early (add-on to patients on ≤1 oral antidiabetic
agent), or later (add-on to ≥2 OADs) in the natural history of T2D. The
authors used data from a pooled analysis of 26-week data from 7
randomised phase 3a and 3b clinical trials (n=4625). They found that HbA1c
was decreased by an average of 1.55% on no or only one drug compared to
a smaller decrease of 1.18% in patients on two or more oral drugs
(P<0.0001). If use of liraglutide earlier in diabetes makes sense, perhaps
using for weight loss in obese, non-diabetics might also be effective. In
the SCALE maintenance phase III trial . 422 non-diabetic obese patients
were randomized to either 3 mg/day of liraglutide or placebo to maintain
weight loss achieved in a previous four- to 12-week low-calorie diet where
they had already lost at least 5% of their body weight. One year later, there
was a greater percentage of patients on liraglutide that maintained the
weight they lost compared to placebo (81% versus 49%, P<0.0001). In
addition, more patients taking liraglutide lost an additional 5% of their body
weight or more (51% versus 22%, P<0.001), and their mean weight loss was
6.1% compared with just 0.5% for placebo patients (P<0.0001).
From Medscape Education Clinical Briefs
Updated Treatment Guidelines Issued for Diabetes Management
News Author: Miriam E. Tucker 02/24/2016
http://www.medscape.org/viewarticle/859189?nlid=103927_2705&src=wnl_cmemp_160425_mscpedu_imed&impID=1074254&faf=1

*Combination therapy is usually needed and

should include agents with complementary
mechanisms of action.
* Lifestyle optimization should not delay needed
pharmacotherapy; medications can be started
simultaneously and adjusted based on response to
lifestyle intervention. HbA1c target should be
individualized based on specific patient factors.
Safety is the top priority for any antidiabetic
therapy, and minimizing the risk for weight gain is
also a priority.
From Medscape Education Clinical Briefs
Updated Treatment Guidelines Issued for Diabetes Management
News Author: Miriam E. Tucker 02/24/2016
http://www.medscape.org/viewarticle/859189?nlid=103927_2705&src=wnl_cmemp_160425_mscpedu_imed&impID=1074254&faf=1

*A physical activity regimen for patients without

contraindications should involve at least 150
minutes per week of moderate-intensity exercise
and strength training
* Lower caloric intake is the main driver for weight
loss. Structured counseling and meal replacement
programs are more effective than standard in-office
counseling.
*Behavioral support includes structured weight loss
and physical activity programs, support from family
and friends, and community groups encouraging a
healthy lifestyle through emotional support and
motivation.
 file:///C:/Users/
ULLOQUE/Desktop/
DIABETES%20%20ADA
%20%202016%20(2).pdf

AMERICAN DIABETES
ASSOCIATION STANDARDS
OF MEDICAL CARE IN
DIABETES 2016
 JOVENES :
chateen, twitteen, jueguen,
……..
pero también
ESTUDIENNNNN………