Tipos de diabetes

Diabetes monogénica
Biopatologia_2020
Joana Guimarães
Definição de Diabetes

Resulta da deficiência, absoluta ou rela3va, de insulina, consequente à ineficiência

da sua ação a nível dos tecidos, da deficiência da sua secreção ou de ambas. Daí

resulta perturbação do metabolismo dos HC, lípidos e proteínas, sendo a

consequência mais evidente, a hiperglicemia.

Diagnós(co
Classificação
Diabetes )po 1 - e)opatogenia
• Type 1 diabetes is a chronic disease in which gene3c predisposi3on, coupled with environmental
influences predominantly early in life, induces pancrea3c beta cell autoimmunity eventually
resul3ng in both loss of func3on and destruc3on.

• The loss of beta cells leads to gradually diminishing insulin produc3on, loss of blood sugar control
and subsequent dependence on exogenous insulin administra3on;

Diabetologia (2017) 60:1370–1381

 Gené%ca
• Type 1 diabetes is a heritable polygenic disease with iden5cal twin concordance of 30–70%,
sibling risk of 6–7%, and a risk of 1–9% for children who have a parent with diabetes.

• 3% of pa5ents have a first-degree rela5ve with type 1 diabetes;

• The risk of type 1 diabetes depends on which family members are affected: 3% if the mother,
5% if the father and 8% if a sibling has type 1 diabetes ;

• Close to 100 gene5c loci have been associated with suscep5bility to type 1 diabetes;

• Varia5ons in the HLA region account for about half of the familial gene5c risk ;
Fatores ambientais
• The incidence of type 1 diabetes has increased by several 5mes over the past 30 years.

• This increase can only be explained by changes in environment or lifestyle. Suppor5ng the impact
of environment or lifestyle on risk, migrants tend to adcquire the same risk of type 1 diabetes as
the popula5on in their new area of residence.

• In Europe, the risk of type 1 diabetes differs substan5ally in people who are gene5cally close but
separated by socioeconomic borders.

• Improved understanding for the environmental determinants of type 1 diabetes could make it
possible to prevent or delay the disease.
Lancet. 2016 June 04; 387(10035): 2340–2348
Model of the pathogenesis and natural history of type 1
diabetes.

Mark A. Atkinson Cold Spring Harb Perspect Med

2012;2:a007641
Clínica
Diabetes )po 2
• Type 2 diabetes is the most common type of diabetes, accoun4ng for around 90% of all diabetes
cases.

• Is most commonly diagnosed in older adults, but is increasingly seen in children, adolescents and
younger adults due to rising levels of obesity, physical inac4vity and poor diet.

• 40–70% of BMI varia4on is explained by gene4c factors and, similarly, the increase in type 2
diabetes risk associated with having a sibling with type 2 diabetes is two- to threefold .

• Although the gene4c architecture might par4ally determine an individual’s response to

environmental changes, the main drivers of the global epidemic of T2DM are the rise in obesity, a
sedentary lifestyle, energy-dense diets and popula4on ageing.
Diabetologia (2014) 57:1528–1541
Outros (pos de diabetes
Diabetes monogénica
• Monogenic diabetes results from one or more defects in a single gene. The disease may be inherited within
families as a dominant, recessive, or non-Mendelian trait or may present as a spontaneous case due to a de
novo muta<on (ie, not inherited from parents)
• 40 different gene<c subtypes of monogenic diabetes have been iden<fied to date, each having a typical
phenotype and a specific paCern of inheritance.
• Iden<fica<on of children with monogenic diabetes usually improves their clinical care. Making a specific
molecular diagnosis helps predict the expected clinical course of the disease and guide the most appro-
priate management in a par<cular pa<ent, including pharmacological treatment.
• It has important implica<ons for the family as it enables gene<c counseling and frequently triggers extended
gene<c tes<ng in other family members with diabetes or hyperglycemia who may also carry a causal
muta<on, thereby improving classifica<on of diabetes.
• Molecular gene<c tes<ng is both sensi<ve and specific for diagnosing monogenic diabetes
Outros (pos de diabetes – Defeito secreção insulina
Diabetes neonatal
• Teste gené)co: em todos os
casos de DM < 6 meses e entre
6-12 meses se dúvidas no
diagnós)co (acs nega)vos, por
exemplo)

• Peso baixo para idade

gestacional (devido a
deficiência de insulina)

• Pode ser transitória ou

permanente

• Manifestações associadas
Outros (pos de diabetes – Defeito secreção insulina
MODY
• The diagnosis of MODY should be suspected in cases with:
• A family history of diabetes in one parent and first-degree rela?ves of that affected parent in pa?ents
who lack the characteris?cs of type 1 diabetes (no islet autoan?bodies, low or no insulin requirements
more than 5 years aHer diagnosis [s?mulated C-pep?de >200 pmol/L]) and lack the characteris?cs of
type 2 diabetes (marked obesity, acanthosis nigricans).
• Mild stable fas?ng hyperglycemia which does not progress. Such cases should be tested for glucokinase
gene muta?ons (GCK-MODY), which is the commonest cause of persistent, incidental hyperglycemia in
the pediatric popula?on
• Specific features can suggest subtypes of MODY, such as renal developmental disease or renal cysts (HNF1B-
MODY) and macrosomia and/or neonatal hypoglycemia (HNF4A-MODY)
• In familial autosomal dominant symptoma?c diabetes, muta?ons in the hepatocyte nuclear factor 1α
(HNF1A) gene (HNF1A- MODY) should be considered as the first diagnos?c possibility, while muta?ons in the
glucokinase gene (GCK-MODY) are the most common cause in the absence of symptoms or marked
hyperglycemia.
 OUTROS TIPOS DE DIABETES – DEFEITO SECREÇÃO INSULINA

• DNA mitocondrial
• Maternally transmi3ed
• An A-to-G transi6on in the mitochondrial transfer RNA Leu(UUR) gene at base pair 3243
• Associated with sensorineural hearing
• The mitochondrion plays a key role in the regula6on of insulin secre6on, par6cularly in
response to glucose. Abnormal insulin secre6on may be seen in subjects with this
mitochondrial muta6on, even if diabetes has not yet developed and glucose tolerance is
normal or impaired.

• MELAS (Mitochondrial encephalomyopathy, lac6c acidosis, and stroke-like episodes)

Nat Rev Endocrinol. 2017 Feb;13(2):92-104.

Outros (pos de diabetes – defeito ação insulina
Endocrine Reviews 32: 498–514, 2011
Leprechaunismo ou S.Donohue
Síndrome de Rabson-Mendenhall
Outros Síndromes Gené0cos
• Síndrome de Down
• S. Klinefelter
• S. Turner
• S. Wolfram
• Ataxia de Fridreich
• Coreia de Hun=ngton
• S. Lawrence-Moon-Biedel
• Distrofia miotónica
• PorGria
• S. Prader-Willi
• Outros
Diabetes na criança e adolescente
 Bibliografia
• Lemelman, M. B., Letourneau, L., & Greeley, S. A. W. (2018). Neonatal Diabetes Mellitus: An Update on
Diagnosis and Management. Clinics in Perinatology, 45(1), 41–59.
• ISPAD Clinical PracNce Consensus Guidelines 2018: DefiniNon,epidemiology, and classificaNon of diabetes in
children and adolescentes. Pediatric Diabetes October 2018; 19 (Suppl. 27): 7–19.
• ISPAD Clinical PracNce Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for
children, adolescents, and young adults with diabetes. Pediatric Diabetes October 2018; 19 (Suppl. 27): 105–
114.
• ISPAD Clinical PracNce Consensus Guidelines 2018: Insulin treatment in children and adolescents with
diabetes. Pediatric Diabetes October 2018; 19 (Suppl. 27): 115–135.
• www.endotext.org