ISCHEMIC STROKE / PREVENTION / RISK FACTORS
Diabetes mellitus
Created 20/02/2023, last revision 09/04/2023
AHA/ASA guidelines 2014 – secondary stroke prevention |
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Definition
- diabetes is a syndrome characterized by the inability of the body to process glucose and maintain its levels within physiological limits due to absolute (↓ secretion) or relative insulin deficiency (↑ resistance), resulting in altered glycide, fat, and protein metabolism
- it is a heterogeneous group of diseases that accelerates the development of atherosclerosis and potentiates the development of microangiopathy; the increased risk of thrombotic events is also related to concomitant dyslipidemia, endothelial dysfunction, platelet hyperreactivity, and impaired fibrinolytic balance
- diabetes increases cardiovascular morbidity and mortality and is an independent risk factor for stroke
- the risk of stroke is 1.8 to 6 times higher compared to the non-diabetic population, and the risk increases with poor compensation
- the risk is higher in the 20-65 year old population (5-14 times higher) [Khoury, 2013]
- patients with DM have a worse prognosis for stroke (3 times higher mortality) and a 2 times higher risk of stroke recurrence
- diabetes is often associated with metabolic syndrome X
- hyperglycemia (DM or impaired GTT), insulin resistance
- dyslipidemia (in DM, typically ↑ TG and LDL)
- arterial hypertension
- abdominal obesity (waist circumference ≥ 102cm in men, ≥ 88cm in women)
- the risk of cardiovascular disease (CVD) is increased in the presence of other vascular risk factors
- management of risk factors associated with metabolic syndrome in type 2 DM (T2DM) is essential for stroke prevention
- absolute – destruction of β-cells of the islets of Langerhans
- relative
- abnormal insulin
- abnormal insulin molecule (mutation)
- defective conversion of preproinsulin to insulin
- circulating antibodies against insulin or the receptor
- insulin resistance of the target tissue
- receptor defect
- post-receptor disorder
- abnormal insulin
Classification
Type 1 diabetes mellitus (T1DM)
- autoimmune (5-10%) x idiopathic (no autoantibodies present)
- defect in insulin secretion; if untreated, associated with ketoacidosis
- most common in adolescents, but also in adults (LADA – Latent Autoimmune Diabetes in Adults), often in non-obese individuals
- exogenous insulin must be administered
- slow-onset T1DM
- diagnosis usually made in individuals > 30 years of age, usually mistaken for T2DM
- positive antibodies (autoimmunity), slower progression and diabetes manifestations are milder
- initially well controlled by diet and PAD, does not lead to diabetic ketoacidosis, but gradually insulin dependence develops (months – years)
Type 2 diabetes mellitus (T2DM)
- mostly in adults
- there is enough endogenous insulin to prevent ketoacidosis, but levels are often either subnormal or relatively inadequate due to low tissue sensitivity (tissue insulin resistance)
- obesity may contribute to resistance
- approx. 5% of T2DM cases
- a group of monogenic diabetic disorders with familial occurrence and a well-defined mode of inheritance (usually AD)
- approx. 6 types (MODY1-6)
- early manifestation (childhood, adolescence or early adulthood)
- independent of obesity, individuals do not have metabolic syndrome
- pathophysiology: genetically determined β-cell dysfunction without evidence of autoimmunity
- MODY due to mutations in glucokinase (MODY2) (responsible for the sensitivity of the β-cell to glycemia)
- MODY due to mutations in transcription of factors responsible for regulating insulin production in the β-cells)
Gestational diabetes mellitus
- a disorder of glucose metabolism that occurs during pregnancy
- it is caused by a transient increase in insulin resistance and usually resolves after delivery
- blood sugar levels are only slightly elevated due to gestational diabetes, so women have no obvious difficulties
- the increased amount of glucose reaches the baby via the placenta, leading to excessive growth and an increased risk of diabetes in adulthood. Mothers are also at increased risk of developing T2DM in later decades
- risk factor:
- age > 30 years
- overweight
- smoking
- family history of DM
- diagnosis is made using an oral glucose tolerance test (oGTT)
- between 24-28 weeks of pregnancy
- in women at risk between 16-18 weeks of pregnancy
Other specific types
- genetic defects of pancreatic B-cells
- monogenic DM type MODY 1-6 (Maturity-onset diabetes of the young) – about 5% of T2DM
- mitochondrial DNA mutations
- genetic defects causing insulin resistance (lipoatrophic DM)
- diseases of the exocrine pancreas (pancreatitis, pancreatic tumor, cystic fibrosis, hemochromatosis)
- endocrinopathies (Cushing’s syndrome, acromegaly, pheochromocytoma, hyperthyroidism, etc.)
iatrogenic DM - other genetic syndromes associated with DM (Down syndrome, Klinefelter syndrome, Turner syndrome)
Diagnostic evaluation
Dg. criteria for diabetes mellitus
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Impaired Fasting Glucose (IFG)
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Impaired glucose tolerance (IGT) |
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Must be confirmed by repeated measurements
Management
→ management of acute hyperglycemia
→ management of acute hypoglycemia
→ continuous insulin therapy protocol
The main goals of long-term diabetes management |
I. Achievement or approaching normoglycemia in the long term
II. Careful compensation of associated risk factors and comorbidities (especially in T2DM)
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- pharmacological treatment differs between type 1 and type 2 diabetes
- T1DM requires insulin treatment
- T2DM treatment starts with lifestyle modification measures and metformin; if the combination of oral antidiabetic drugs and all measures fail to achieve the desired glycemic control, a decision must be made on adding insulin
Target values for metabolic syndrome therapy
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Fasting glycemia ( ≥ 8 h after last meal)
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≤ 6 mmol/L |
Glycemia 1-2 hod. after meal
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≤ 7,5 mmol/L
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HbA1c (glycated hemoglobin)
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non-diabetics < 38 mmol/mol diabetics (well controled) 43-53 mmol/mol |
Blood pressure → arterial hypertension |
< 130/80 mmHg |
Lipids → dyslipidemia | |
Body mass index (BMI) |
19-25 |
Waist circumference (men/women) | < 94 cm / < 80 cm |
The finding of borderline or mildly abnormal renal function (see below) should lead to more intensive treatment of diabetes and arterial hypertension to achieve the best possible compensation
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Non-pharmacological measures
- diet
- diabetic diets with 175 g, 200 g or 225 g of carbohydrates or reduction diets
- limit the intake of animal fats, processed meat (sausages, minced meat, fast food) and juices
- increase intake of vegetable fats, nuts, fiber, coffee, and fish
- physical activity
- take into account age, type of diabetes, weight and presence of associated complications
- e.g. at least 30 minutes of walking per day
- weight reduction of at least 5-10%
Insulin
Peroral antidiabetics (PADs)
- start therapy with the lowest possible dose
- if there is an inadequate response, increase the dose, but do not use the maximum dose; instead, switch to a combination of antidiabetic drugs