CONSEQUENCES OF OBESITY Flashcards
What is the relationship between obesity and life expectancy/all cause mortality?
In summary, at both extremes of weight there is reduced life-expectancy and all-cause mortality.
- the effects of obesity (and underweight) are compounded by smoking
- people who are underweight may have shorter life expectancy due to smoking or other chronic illnesses
- males tend to be impacted at slightly higher BMIs
Obesity and Life Expectancy - Non-Smokers
- Overweight:
- Females lose 3.3 years
- Males lose 3.1 years
- Obese:
- Females lose 7.1 years
- Males lose 5.8 years
- Source: Ann Intern Med 2003;138:24-32
Obesity and Life Expectancy - Smokers
- Overweight Smokers vs. Lean Smokers:
- Females lose 7.2 years
- Males lose 6.7 years
- Obese Smokers vs. Lean Non-Smokers:
- Females lose 13.3 years
- Males lose 13.7 years
- Source: Ann Intern Med 2003;138:24-32
What are consequences for obesity in terms of disease (RR study)?
- BMI vs Hazard ratio
- associated with increased CDs, NCDs; opportunities for injuries and external injury greater with underweight (presumably due to more physical activity)
- note certain cancers are elevated, although some more significant than others
What are the broad categories of conseuquences of obesity?
- Related to Metabolic Syndrome
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Other Medical Consequences:
- E.g., Obstructive sleep apnea, gastro-oesophageal reflux, skin infections
- Increased Malignancy
- Increased Surgical Risk
- Increased Pregnancy Risk
- Psychosocial/Socio-Economic
can also go by system
Provide an overview of MetS
- Insulin Resistance Syndrome
- Syndrome X
Metabolic Syndrome Definition
- Criteria: 3 out of 5
- Elevated waist circumference (ethnic specific)
- WHO criteria (IDF, AHA/NHLBI differ)
- Caucasian: Men ≥ 94 cm, Women ≥ 80 cm
- Asian: Men ≥ 90 cm, Women ≥ 80 cm
- Elevated triglycerides ≥ 1.7 mmol/L
- Low HDL cholesterol
- Men < 1.0 mmol/L, Women < 1.3 mmol/L
- Elevated blood pressure
- Systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg
- Elevated fasting glucose ≥ 5.6 mmol/L
- Source: Circulation 2009; 120:1640-1645
What type of obesity is generally associated with MetS
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Central Pattern of Obesity (visceral or abdominal)
- “Apples” rather than “Pears”
- Increased waist circumference
List the features of MetS and associated clinical syndromes
Metabolic Syndrome - Features
- Insulin resistance with compensatory hyperinsulinaemia
- Obesity (central, visceral)
- Glucose intolerance
- Dyslipidaemia
- Hypertension
- Hyperuricaemia
- Elevated inflammatory markers (C-reactive protein, TNF)
- Coagulation defects (PAI-1 and fibrinogen elevated)
- Microalbuminuria (renal albumin leak)
- Low adiponectin
Metabolic Syndrome - Associated Clinical Syndromes
- Type 2 diabetes and gestational diabetes
- Essential hypertension
- Cardiovascular disease (Stroke/IHD/PVD)
- Polycystic ovary syndrome (PCOS)
- Non-alcoholic fatty liver disease (NAFLD)
- Gout
What is the relatiobsuo between insulin resistance and MetS
Insulin Resistance and Compensatory Hyperinsulinaemia
- Insulin resistance is present if there is a reduced capacity of insulin to reduce blood glucose.
- Insulin resistance by itself does not cause diabetes, as insulin resistance is often compensated for by higher insulin secretion.
Metabolic Syndrome, IGT, and Type 2 Diabetes
- Impaired Glucose Tolerance (IGT) and Type 2 Diabetes (T2D) occur when the pancreatic islet beta-cells fail to compensate for the insulin resistance of the metabolic syndrome.
- T2D:
- Insulin resistance AND islet beta-cell failure.
What do intervention and prevention studies of T2D suggest
- In summary, slows the progression of diabetes with exercise
- prevention studies difficult to translate to real world due to additional support and intensive program to aid lifestyle changes
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Da Qing IGT and Diabetes Study:
- 577 IGT subjects followed for 6 years.
- Incidence of diabetes: 13.3% per annum.
- Intervention – Diet: 33% reduction.
- Intervention – Exercise: 47% reduction.
- Intervention – Diet + Exercise: 38% reduction.
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STOP-NIDDM Acarbose Study:
- 1429 IGT subjects followed for 3.3 years.
- Incidence of diabetes per annum: 12.7% per annum.
- Intervention – Acarbose: 25% reduction.
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Diabetes Prevention Study (USA):
- 3234 IGT subjects followed for 2.8 years.
- Incidence of diabetes: 11% per annum.
- Lifestyle intervention (exercise-weight loss): 58% reduction.
- Metformin: 31% reduction.
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Finnish Study:
- 522 IGT subjects followed for 3.2 years.
- Incidence of diabetes: 9.8% per annum.
- Lifestyle intervention (exercise and weight loss): 58% reduction.
What effect does banding have on obese T2D patients?
- Study: Dixon et al, JAMA 2008;299:316-323
- Participants: 60 Obese (BMI >30 <40) T2D - randomised to lifestyle modification or lap gastric banding.
- Follow Up: 2 years
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Results:
- Remission of T2D: 73% surgical group, 13% lifestyle group.
- Weight Loss: 20.7% (+/- 8.6%) surgical group, 1.7% (+/- 5.2%) lifestyle group.
- Remission of T2D was related to the amount of weight loss and lower baseline HbA1c.
Describe dyslipidaemia as it relates to MetS
- Elevated triglyceride-rich particles (especially post-prandial) (chylomicrons, VLDL) (TG ≥ 1.7 mM)
- Reduced high-density lipoprotein cholesterol (HDL < 1.0 in men and < 1.3 in women)
- Reduced low-density lipoprotein (LDL) particle size - more atherogenic
- Elevated plasma non-esterified fatty acids
Describe the effects of essential hypertension
End-Organ Damage
- Arteries: Aneurysms, atheroma
- Heart: Cardiomyopathy
- Kidneys: Renal impairment/failure
- Brain: Multi-infarct dementia/stroke
Describe the relationship between MetS an obesity with respect to all cause and CV mortality
- Metabolic syndrome exacerbates mortality, including for lean subjects
- Study: Aerobics Center Longitudinal Study (ACLS)
- Source: Katzmarzyk et al. Diabetes Care 2005, 28:91
- Participants: 19173 men followed for 10.2 years
- All-Cause Mortality: Numbers in bars represent death rates per 10,000 person-years of follow-up, adjusted for age and year of examination, numbers in parentheses are the number of deaths.
- CVD Death: ©2005 by American Diabetes Association
Describe presentations of PCOS and its long term complications
Presentations
- Oligomenorrhoea or Amenorrhoea
- Hirsutism - due to increased androgens, inc. acne
- Infertility
- Acanthosis Nigricans: Severe insulin resistance, hyperinsulinaemia - distribution neck and axilla
- Other Features of Metabolic Syndrome
Oligomenorrhoea/Amenorrhoea/Infertility
- Oestradiol: Normal
- High LH/FSH Ratio
- Likely Pathogenesis:
- High ovarian androgen levels converted to oestrogens in periphery suppress pituitary FSH release, preventing ovulation.
- Hyperthecosis causes increased androgen production.
- Vicious cycle: Ovary/pituitary.
Hirsutism
- Increased Ovarian Androgen Secretion
- Low Sex Hormone Binding Globulin (SHBG) - due to increased circulating androgens
- Elevated Free Androgen Index (FAI)
Long-Term Consequences of PCOS
- Increased Gestational Diabetes
- High Progression to Type 2 Diabetes
- High Rates of Cardiovascular Disease
- Other Metabolic Syndrome Related Issues
- note PCOS is not one size fits disease
Describe NAFLD/MASLD and the effect of obesity on long term consequences
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Description:
- Form of fatty liver attributed to over-nutrition and complications such as weight gain, central obesity, insulin resistance, glucose intolerance, atherogenic dyslipidemia, and arterial hypertension (metabolic syndrome), especially in genetically predisposed individuals.
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Prevalence:
- Common and mostly mild (estimate ~25% in Asian regions).
- Advanced liver fibrosis in ~3.7% of those with NAFLD in Asia.
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Severe Cases:
- Non-alcoholic steatohepatitis (NASH) is the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in patients without other known etiological causes of liver disease.
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Pathogenesis:
- Overlapping disease pathogenesis with fibrotic progression in hepatitis C and role of alcohol.
- Source: Wong V et al. Journal of Gastroenterology and Hepatology 33 (2018) 70–85
Long-Term Follow-Up
- Study:
- Over ~12 years, 501 of 1051 subjects with metabolically healthy obesity (MHO) progressed to metabolically unhealthy obesity (MUO).
List some other medical consequences of obesity
- Musculoskeletal: Degenerative arthritis
- Respiratory: Obstructive sleep apnea
- Gastrointestinal: Gastro-oesophageal reflux disorder, cholelithiasis
- Dermatological: Skin infections (e.g., thrush)
- Oncological: Cancer
- Reproductive: Pregnancy risk
- Surgical: Increased surgical risk
