Metabolic Sydrome Flashcards
a constellation of metabolic derangements that increases the risk of developing type 2 diabetes mellitus and cardiovascular disease.
metabolic syndromes
The key feature of metabolic syndrome is
insulin resistance
Insulin resistance (IR) and the resultant hyperinsulinemia lead directly or indirectly to the development of
hypertension, glucose intolerance and dyslipidemia.
Obesity, especially____ obesity, exacerbates the insulin resistance. Insulin resistance has a strong genetic component.
central
What three factors define metabolic syndrome?
- Abdominal obesity: waist circumference with >40 men and >35 women
- Hypertriglycidemia: >150 with LOW HLD
- HYpertentsion: > 130/85
What is the role of increased adiposity in insulin resistance?
big fat cells make lots of endocrine hormones, increase FFA, impair glucose uptake to muscles (bc muscles take up fat instead) and leads to insulin resistance
Increases in circulating glucose, and to some extent FFA, increase pancreatic insulin secretion, resulting in ______ which may result in enhanced sodium reabsorption and increased sympathetic nervous system (SNS) activity
hyperinsulinemia
The enhanced secretion of ______ and _______ produced by adipocytes and monocyte-derived macrophages results in more insulin resistance and lipolysis of adipose tissue triglyceride stores to circulating FFAs.
interleukin 6 (IL-6)
tumor necrosis factor (TNF- )
Insulin resistance and hyperinsulinemia are considered to be the key pathogenic factors in the development of the
metabolic syndrome.
-Insulin resistance tends to involve primarily
fat and muscle tissue.
The ________ can often delay the development of diabetes (at least early on) by producing enough insulin to overcome the insulin resistance (hyperinsulinemia)
endocrine pancreas
production of several ______ by adipose tissue in obese people is abnormal and contributes to insulin resistance and cardiovascular disease risk.
adipokines (including inflammatory cytokines)
. Initially, the β-cells of the pancreas compensate for insulin resistance by increasing ______ and release (hyperinsulinemia).
However, prolonged stimulation of beta-cell leads to____such that insulin levels decrease – this leads to frank hyperglycemia (type 2 diabetes mellitus).
insulin synthesis
“beta-cell failure”
Adiponectin and leptin_____ with insulin resistance.
TNFα and resistin_____ with insulin resistance.
decrease
increase
What are the two possible mechanisms for insulin resistance?
Inflammation: lipids make cytokines which attrack shit to block the insulin receptor substrate
Lipid overload: see increase fat uptake into the muscles with produce DAGS that will block insulin receptor
decreases in ____function leads to a decrease in insulin-mediated glucose uptake leading to hyperglycemia
IRS-1
Insulin resistance leads to hyperinsulinemia causing: HTN, thrombosis, dyslipidemia and glucose tolerace all contributing to:
Vascular/heart disease
Risk factors for obesity:
Low socioeconomic status
Lack of physical activity/sedentary lifestyle
High carbohydrate diet
Smoking
Genetic predisposition
Use of atypical antipsychotics,
Complications associated with metabolic syndrome
- Fatty liver disease (nonalcoholic steatohepatitis or NASH)\
- Polycystic ovary syndrome
- Obstructive sleep apnea
- Gout (Hyperuricemia)
- Increased risk of cancer
-The typical lipid profile in the metabolic syndrome is a___ HDL,___ triglycerides and ______ in the LDL cholesterol. The LDL particles are smaller and more atherogenic
low
elevated
mild or moderate increase
What do we see with VLDL levels and lipoprotein lipase in people with insulin suppresion
The suppression of lipoprotein lipase and very-low-density lipoprotein (VLDL) production by insulin is defective in insulin resistance, leading to increased flux of free fatty acids (FFAs) to the liver and increased VLDL production, which results in increased circulating triglyceride concentrations.
In insulin resistance, the inability of insulin to suppress lipolysis in adipose tissue and glucagon secretion by alpha cells in the islet results in
increased gluconeogenesis
Key lifestyle modifications to tx metabolic syndrome
diet, exercise, stop smoking, physical activity, bariatric surgery
