Diabetes Mellitus. Prevenção e Terapeutica UP7

(1)

Diabetes Mellitus

(2)

(3)

(4)

(5)

(6)

(7)

(8)

(9)

(10)

Diabetes Mellitus tipo 2

Factores de risco

 • Obesidade, alimentação inadequada e inactividade física;

 • Envelhecimento;

 • História familiar de diabetes;

 • Diabetes gestacional (quer para o bébé, quer para a mãe);

 • Etnia.



Muitos são portadores da doença sem o saberem!!!



Muitas vezes diagnosticados devido ao aparecimento de complicações da doença.



Muitas vezes associada à obesidade.

(11)

Recommendations: Testing for Diabetes in

Asymptomatic Patients

• Consider testing overweight/obese adults with

one or more additional risk factors

–

In those without risk factors, begin testing at age 45

years (B)

• If tests are normal

–

Repeat testing at least at 3-year intervals (E)

• Use A1C, FPG, or 2-h 75-g OGTT (B)

• In those with increased risk for future diabetes

–

Identify and, if appropriate, treat other CVD risk factors

(B)

(12)

Criteria for Testing for Diabetes in

Asymptomatic Adult Individuals (1)

• Physical inactivity

• First-degree relative with diabetes

• High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)

• Women who delivered a baby weighing >9 lb or were diagnosed with GDM

• Hypertension (≥140/90 mmHg or on therapy for hypertension)

• _{HDL cholesterol level}

<35 mg/dl (0.90 mmol/l) and/or a triglyceride level >250 mg/dl (2.82 mmol/l)

• _{Women with polycystic ovarian} syndrome (PCOS)

• _{A1C ≥5.7%, IGT, or IFG on} previous testing

• _{Other clinical conditions}

associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)

• _{History of CVD}

*At-risk BMI may be lower in some ethnic groups.

1. Testing should be considered in all adults who are overweight (BMI

≥25 kg/m

2

_{*) and have additional risk factors:}

(13)

2. In the absence of criteria (risk factors on previous

slide), testing for diabetes should begin at age 45

years

3. If results are normal, testing should be repeated at

least at 3-year intervals, with consideration of more

frequent testing depending on initial results and risk

status

ADA. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S14. Table 4.

Criteria for Testing for Diabetes in

Asymptomatic Adult Individuals (2)

(14)

DPP: Managing Prediabetes

• For those found to have prediabetes, provide

support or referral to encourage

• Weight loss of at least 7%

• Moderate exercise of at least 150 minutes

per week

• Consider metformin for certain patients

• Obese (BMI ≥35 kg/m

2

)

• <60 years (most effective, 25-44 years)

• Lifestyle interventions feasible, more

cost-effective than medications

(15)

Objectivos da Terapia



Melhorar os sintomas de hiperglicémia



Reduzir o inicio e progressão de complicações microvasculares e macrovasculares



Reduzir mortalidade



Melhorar a qualidade de vida



Níveis desejáveis de glucose e hemoglobina glicosilada (A1C)

Tratamento

Necessário controlar factores de risco de DCV : tabaco, deslipidémias, PA

Necessário atingir objectivos :



glicémia, monitorização adequada pelo próprio



pressão arterial



níveis lipídicos



monitorizações regulares de complicações

(16)

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

3. ANTI-HYPERGLYCEMIC THERAPY

• Glycemic targets

-

HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9 mmol/l])

-

Pre-prandial PG <130 mg/dl (7.2 mmol/l)

-

Post-prandial PG <180 mg/dl (10.0 mmol/l)

-

Individualization is key:



_{Tighter targets (6.0 - 6.5%) - younger, healthier}



_{Looser targets (7.5 - 8.0%}

+

_{) - older, comorbidities,}

hypoglycemia prone, etc.

-

Avoidance of hypoglycemia

(17)

Terapia anti-hiperglicémica

Os objectivos devem ser individualizados de acordo com:

• Duração da Diabetes

• Idade/ esperança de vida

• As comorbidades

• CVD conhecida e outras complicações microvasculares

(18)

Class

Mechanism

Advantages

Disadvantages

Cost

Biguanides • Activates AMP-kinase

•  Hepatic glucose production • Extensive experience • No hypoglycemia • Weight neutral • ?  CVD • Gastrointestinal • Lactic acidosis • B-12 deficiency • Contraindications Low SUs / Meglitinides

• Closes KATP channels

•  Insulin secretion • Extensive experience •  Microvasc. risk • Hypoglycemia • Weight gain • Low durability • ? Ischemic preconditioning Low TZDs • PPAR-g activator •  insulin sensitivity • No hypoglycemia • Durability •  TGs,  HDL-C • ?  CVD (pio) • Weight gain

• Edema / heart failure • Bone fractures • ?  MI (rosi) • ? Bladder ca (pio) High a-GIs • Inhibits a-glucosidase • Slows carbohydrate absorption • No hypoglycemia • Nonsystemic •  Post-prandial glucose • ?  CVD events • Gastrointestinal • Dosing frequency • Modest  A1c Mod.

(19)

Class

Mechanism

Advantages

Disadvantages Cost

DPP-4 inhibitors • Inhibits DPP-4 • Increases GLP-1, GIP • No hypoglycemia • Well tolerated • Modest  A1c • ? Pancreatitis • Urticaria High GLP-1 receptor agonists • Activates GLP-1 R •  Insulin,  glucagon •  gastric emptying •  satiety • Weight loss • No hypoglycemia • ? Beta cell mass • ? CV protection • GI • ? Pancreatitis • Medullary ca • Injectable High Amylin mimetics • Activates amylin receptor •  glucagon •  gastric emptying •  satiety • Weight loss •  PPG • GI • Modest  A1c • Injectable • Hypo w/ insulin • Dosing frequency High Bile acid sequestrants

• Bind bile acids

•  Hepatic glucose production • No hypoglycemia • Nonsystemic •  Post-prandial glucose •  CVD events • GI • Modest  A1c • Dosing frequency High Dopamine-2 agonists • Activates DA receptor • Modulates hypothalamic control of metabolism •  insulin sensitivity • No hypoglyemia • ?  CVD events • Modest  A1c • Dizziness/syncope • Nausea • Fatigue High

(20)

Class

Mechanism

Advantages

Disadvantages

Cost

Insulin • Activates insulin

receptor •  peripheral glucose uptake • Universally effective • Unlimited efficacy •  Microvascular risk • Hypoglycemia • Weight gain • ? Mitogenicity • Injectable • Training requirements • “Stigma” Variable

(21)

Long (Detemir)

Rapid (Lispro, Aspart, Glulisine)

Hours

Long (Glargine)

0 2 4 6 8 10 12 14 16 18 20 22 24

Short (Regular)

Hours after injection

Ins u lin lev e l Intermediate (NPH)

Terapia anti-hiperglicémica

Insulina

NPH

Regular

Basal analogues (Glargine, Detemir)

Rapid analogues (Lispro, Aspart, Glulisine)

Pre-mixed varieties

(22)

Insulinoterapia

Ajuste da dose:



Ingestão de HC



Exercício

Aspectos das insulinas a considerar:



Inicio de acção



Pico de acção



Duração de acção

(23)

Insulinoterapia

Terapia anti-hiperglicémica na Diabetes Mellitus tipo 1

Replicar o perfil fisiológico da insulina

Objectivo

Componente Basal

Insulina de acção intermédia ou longa (Detemir 2x ao dia, Glargine 1x ao dia)

Atenção: com excepção da glargina têm um efeito de pico que deve ser tido em conta

no planeamento das refeições e das actividades.

Componente Bolus



Insulina de acção rápida e curta duração (Lispro, aspart, glulisina)



Ajuste da dose de acordo com os níveis de glicémia pré-prandiais, nível da actividade seguinte e antecipação da ingestão em HC.

(24)

Insulinoterapia

(25)



Pacientes com A1C ≤ 7% são tratados com medidas de alteração de estilo de vida com ou sem insulin sensitizer.



Pacientes com 7<A1C<8 são tratados com um agente oral



Pacientes com A1C>8 são tratados com dois agentes orais ou insulina.



A maioria dos pacientes com A1C>9 até 10 necessitam de 2 ou mais agentes para atingir os objectivos de glicémia.

(26)

(27)

(28)

(29)

Diabetes Care, Diabetologia.

(30)

(31)

(32)

Guidelines for Glycemic, BP, & Lipid Control

American Diabetes Assoc. Goals

HbA1C

< 7.0% (individualization)

Preprandial

glucose

70-130 mg/dL (3.9-7.2 mmol/l)

Postprandial

glucose

< 180 mg/dL

Blood pressure

< 130/80 mmHg

Lipids

LDL: < 100 mg/dL (2.59 mmol/l)

< 70 mg/dL (1.81 mmol/l)

(with overt CVD)

HDL: > 40 mg/dL (1.04 mmol/l)

> 50 mg/dL (1.30 mmol/l)

TG: < 150 mg/dL (1.69 mmol/l)

ADA. Diabetes Care. 2012;35:S11-63

HDL = high-density lipoprotein; LDL = low-density lipoprotein; PG = plasma glucose; TG = triglycerides.