weeks 4-6

Insulin Resistance and the Metabolic Syndrome

• The clustering of multiple risk components within the metabolic syndrome is thought to occur as a result of obesity (specifically abdominal obesity) and insulin resistance
• Insulin resistance is a hallmark of chronic health risk, but not all obese or insulin-resistant individuals develop the metabolic syndrome
• Gradual decreases in cardiometabolic health can occur long before an individual reaches obesity or is diagnosed as insulin resistant

Insulin Signalling and Glucose Uptake

• In healthy, insulin-sensitive individuals, glucose stimulates the release of insulin from pancreatic beta cells, which reduces plasma glucose concentration through suppression of hepatic glycogenolysis and gluconeogenesis and simultaneous glucose uptake, utilization, and storage by the liver, muscle, and adipose tissue
• Conversely, under conditions of insulin resistance, there is a chronic failure of insulin to maintain glucose homeostasis

Obesity and Adiposity Distribution Abnormalities

• Obesity is an independent risk factor for insulin resistance, hyperglycaemia, hypercholesterolaemia, and hypertension
• Abnormal fat distribution and partitioning may be the pathophysiologic link between obesity and the metabolic syndrome
• Accumulation of fatty acids in non-adipose tissue depots is associated with skeletal muscle insulin resistance

Mitochondrial Dysfunction

• Mitochondrial dysfunction is implicated in the aetiology of insulin resistance, metabolic syndrome, and diabetes
• Obese, sedentary, and insulin-resistant individuals have smaller and fewer mitochondria with impaired function
• Diminished mitochondrial density and function may lead to or coincide with decreased or incomplete lipid oxidation and subsequent accumulation of lipid metabolites, impaired insulin signalling, metabolic inflexibility, and oxidative stress

Proinflammatory and Prothrombotic Characteristics

• Adipose tissue is a dynamic organ that secretes adipocyte-derived hormones and cytokines, contributing to insulin resistance
• Ectopic adiposity is known to play a role in secreting proinflammatory cytokines (e.g., TNF-α and IL-6) and adipocytokines (e.g., leptin, resistin, and adiponectin)
• Elevated levels of hs-CRP are associated with ASCVD and inversely associated with vigorous physical activity

Exercise Prescription Summary

• Cardiorespiratory exercise and resistance exercise are effective for improving cardiometabolic health, independent of weight loss
• Exercise prescription should include gradual progression in duration and intensity, with a minimum of 2-3 non-consecutive days per week
• Range of motion exercise may be included as an adjunct modality to supplement cardiorespiratory and resistance exercise

Exercise Training

• Exercise training, particularly cardiorespiratory exercise, is effective for improving metabolic disturbances, independent of weight loss
• Resistance exercise is effective for enhancing muscle function, insulin sensitivity, and fatty acid oxidation, and for decreasing visceral adiposity
• Combining diet-induced energy restriction and resistance training has been shown to prevent loss in muscle tissue

Monitoring and Recording Blood Glucose Levels

• Monitoring blood glucose levels before and after exercise can allow for early detection of hypoglycaemia or hyperglycaemia, and help determine appropriate pre-exercise blood glucose levels to lower the risk of these conditions.
• Monitoring can also identify those who can benefit from monitoring during and after exercise, provide information for modifying the exercise prescription, and allow for better adjustment of diabetes regimens to manage all activities.
• Monitoring can motivate patients to remain more active to better manage their diabetes.

Exercise and Diabetes Management

• Exercise is a vital component of diabetes management and is considered a method of treatment for type II diabetes because it can improve insulin resistance.
• Although exercise alone is not considered a method of treating type I diabetes, it is still an important part of a healthy lifestyle for people in this group.
• Exercise performed at an intensity below the threshold for an increase in maximal oxygen uptake can be beneficial to health in persons with chronic diseases like diabetes.

Complications of Diabetes

• Chronic complications of diabetes include peripheral neuropathy, which can cause sensory symptoms, muscle weakness, and foot deformities, placing patients at high risk for foot trauma and injury.
• Peripheral neuropathy can also change gait and balance, increasing the risk of falling, but balance training may help lower this risk.
• Diabetic autonomic neuropathy can occur in any system of the body, affecting the ability to perform exercise, and may be manifested by high resting heart rate, attenuated exercise heart rate response, and abnormal blood pressure.

Goal Times and Glycaemic Recommendations

• Goal times for blood glucose levels are critical for people with diabetes.
• Glycaemic recommendations for non-pregnant adults with diabetes include maintaining blood glucose levels as close to normal as possible.

Signs and Symptoms of Diabetes

• Classic symptoms of diabetes include polydipsia, polyuria, and polyphagia.
• Other symptoms of diabetes include unexplained weight loss, infections and cuts that are slow to heal, blurry vision, and fatigue.
• Many people with diabetes may remain asymptomatic, and about one-fourth of those with diabetes do not know they have the disease.

History and Physical Examination

• Patients with diabetes should have an annual physical examination to evaluate for potential indicators of complications, including elevated resting heart rate, loss of sensation or reflexes, and foot sores or ulcers.
• Exercise testing may be appropriate before beginning an exercise program.
• Prior to each exercise training session, healthcare professionals should inquire about the patient's starting blood glucose level, timing and amount of most recent food intake, and medication use and timing.

Resistance Exercise

• Resistance training programs can improve cardiovascular function, insulin sensitivity, strength, and body composition in people with diabetes.
• Resistance training exercises should be done 2-3 days per week on non-consecutive days, and progression of intensity, frequency, and duration should occur slowly.

Range of Motion and Balance Exercise

• Range of motion exercises can be included as part of an exercise program, but should not be substituted for aerobic or resistance exercise.
• Balance training is recommended for all individuals over the age of 40, as it reduces the risk of falls in people with diabetes, even with peripheral neuropathy.

Exercise Prescription Summary

• Exercise training considerations for diabetes include the importance of promoting blood glucose uptake by the skeletal muscles.
• Benefits for people with diabetes are seen with both acute and chronic cardiorespiratory and resistance exercise training.
• Acute bouts of exercise can improve blood glucose, particularly in those with type II diabetes.

Polycystic Ovarian Syndrome (PCOS)

• PCOS is an endocrinopathy of uncertain aetiology, affecting 4-20% of women of reproductive age.

Clinical Features

• PCOS is characterized by:
  • Menstrual abnormalities (oligomennorhea or amenorrhea)
  • Hirsutism
  • Acne
  • Alopecia
  • Anovulatory infertility
  • Recurrent miscarriages

Endocrine Features

• PCOS is associated with:
  • Elevated androgens
  • Luteinising hormone
  • Oestrogen
  • Prolactin

Metabolic Features

• PCOS often includes:
  • Insulin resistance
  • Obesity
  • Lipid abnormalities
  • Increased risk for impaired glucose tolerance and T2DM

Prevalence of Common Features

• Menstrual disturbances:
  • 30% of women with PCOS have normal menses
  • 85-90% of women with oligomenorrhea have PCOS
  • 30-40% of women with amenorrhea have PCOS
• Infertility affects 40% of women with PCOS
• 90-95% of anovulatory women presenting to infertility clinics have PCOS
• Spontaneous abortion occurs in 42-73% of women with PCOS

Risk Factors

• Risk factors for PCOS in adults include:
  • T1DM
  • T2DM
  • GDM

Common Comorbidities

• Insulin resistance affects 50-70% of women with PCOS, leading to:
  • Metabolic syndrome
  • Hypertension
  • Dyslipidaemia
  • Glucose intolerance
  • Diabetes
• Women with PCOS are more likely to have increased coronary artery calcium scores
• Mental health disorders, including:
  • Depression
  • Anxiety
  • Bipolar disorder
  • Binge eating disorder

Diagnostic Criteria

• Diagnosis of PCOS requires at least two of the following characteristics:
  • Clinical or biochemical hyperandrogenism
  • Anovulatory menstrual dysfunction
  • Polycystic ovaries on ultrasound
• Insulin resistance is strongly implicated in the aetiology of PCOS, although not included in the diagnostic criteria

Pathophysiology

• The pathophysiology of PCOS is complex and multifactorial, involving:
  • Unique defect in insulin action and secretion
  • Primary neuroendocrine defect
  • Defect of androgen synthesis
  • Alteration in cortisol metabolism
• A familial pattern in some cases suggests a genetic component, but the candidate genes are yet to be identified

Economic Burden

• PCOS costs the USA healthcare system $4.4 billion annually, with:
  • 40% attributed to treating reproductive dysfunction
  • 40% attributed to PCOS-related diabetes

Pharmaceutical Intervention

• Pharmaceutical treatment for PCOS focuses on addressing reproductive dysfunction and insulin resistance, using:
  • Oral contraceptives
  • Spironolactone
  • Finasteride
  • Fertility treatments, including ovulation induction agents and assisted reproductive technology
  • Metformin

Exercise Intervention

• There are currently no evidence-based exercise guidelines for the treatment of PCOS, and exercise prescription should be individualized to the patient based on presentation and clinical features/comorbidities
• Exercise intervention in women with PCOS has been shown to:
  • Increase follicle-stimulating hormone
  • Increase sex hormone-binding globulin
  • Decrease total testosterone
  • Decrease androstenedione
• The most consistent improvements were demonstrated in:
  • Weight loss
  • Insulin resistance
  • Reproductive function
• Women with PCOS should be advised to engage in at least 90 minutes of aerobic activity per week at a moderate intensity to achieve improved reproductive and cardiometabolic outcomes.

Obstructive Sleep Apnoea (OSA)

• OSA is a sleep disorder where a person's breathing is interrupted during sleep
• OSA is associated with various conditions, including:
  • Hypertension
  • CVA
  • MI
  • Cor pulmonale
  • Motor vehicle accidents

Physical Examination

• The physical examination can suggest increased risk of OSA and should include evaluation of:
  • Respiratory system
  • Cardiovascular system
  • Neurological system
• Particular attention should be paid to:
  • Obesity
  • Upper airway narrowing
  • Other disorders that can contribute to OSA development or consequences

Physical Examination Features

• Features to be evaluated that may suggest OSA presence:
  • Increased neck circumference (> 17 inches in men, > 16 inches in women)
  • BMI ≥ 30
  • Modified Mallampati score of 3 or 4
  • Retrognathia
  • Lateral peritonsillar narrowing
  • Macroglossia
  • Tonsillar hypertrophy
  • Elongated or enlarged uvula
  • High arched or narrow hard palate
  • Nasal abnormalities

Objective Testing

• Following history and physical examination, patients can be stratified according to OSA disease risk
• High-risk patients should have the diagnosis confirmed and severity determined with objective testing
• Severity of OSA must be established to make an appropriate treatment decision
• Objective testing methods:
  • In-laboratory polysomnography
  • Home testing with portable monitors

Polysomnography

• Polysomnography requires the following physiologic signals:
  • Electroencephalogram (EEG)
  • Electrooculogram (EOG)
  • Chin electromyogram
  • Airflow
  • Oxygen saturation
  • Respiratory effort
  • Electrocardiogram (ECG) or heart rate
• Additional recommended parameters:
  • Body position
  • Leg EMG derivations

Portable Monitors

• Portable monitors should, at a minimum, record:
  • Airflow
  • Respiratory effort
  • Blood oxygenation
• Portable monitors may be used in the unattended setting as an alternative to polysomnography for the diagnosis of OSA in patients with a high pre-test probability of moderate to severe OSA and no comorbid sleep disorder or major comorbid medical disorder

Categorisation of Severity

• The measure of severity of OSA is based on the number of apnoea or hypopnoea events per hour of sleep, represented by the Apnoea Hypopnoea Index (AHI)
• Parameters for OSA:
  • Normal: AHI < 5
  • Mild: AHI ≥ 5 and < 15
  • Moderate: AHI ≥ 15 and < 30
  • Severe: AHI ≥ 30

Treatment - PAP

• The American Academy of Sleep Medicine recommends the use of continuous positive airway pressure (CPAP) or oral appliances for treating mild to moderate OSA
• CPAP is recommended as the first-line, and oral appliances as second-line, treatments for severe OSA
• CPAP provides pneumatic splinting of the upper airway and is effective in reducing the AHI
• PAP may be delivered in continuous, bilevel, or autotitrating modes, with additional options for pressure relief and BPAP/APAP modes

Treatment - Behavioural Strategies

• Behavioural treatment options:
  • Weight loss
  • Exercise
  • Positional therapy
  • Avoidance of alcohol or sedatives before bedtime
• Successful dietary weight loss may improve the AHI in obese patients with OSA
• Sleep position can affect airway size and patency, with a decrease in the area of the upper airway, particularly in the lateral dimension, while in the supine position
• Positional therapy consists of a method that keeps the patient in a non-supine position, using a positioning device (e.g., alarm, pillow, backpack, or tennis ball)

Treatment - Oral Appliances

• Custom-made oral appliances may improve upper airway patency during sleep by enlarging the upper airway and/or by decreasing upper airway collapsibility
• Mandibular repositioning appliances (MRA) cover the upper and lower teeth and hold the mandible in an advanced position with respect to the resting position
• Tongue retaining devices (TRD) hold only the tongue in a forward position with respect to the resting position, without mandibular repositioning
• Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to CPAP, or who do not respond to CPAP, are not appropriate candidates for CPAP, or who fail CPAP or behavioural measures

Treatment - Surgical

• Surgical therapy includes a variety of upper airway reconstructive or by-pass procedures, often site-directed and/or staged
• Evaluation for primary surgical treatment can be considered in patients with mild OSA who have severe obstructing anatomy that is surgically correctable
• Surgical procedures may be considered as a secondary treatment for OSA when the outcome of PAP therapy is inadequate, such as when the patient is intolerant of PAP, or PAP therapy is unable to eliminate OSA

Adjunctive Therapies - Bariatric Surgery

• Bariatric surgery is an effective means to achieve major weight loss and is indicated in individuals with a BMI ≥ 40 or those with a BMI ≥ 35 with important comorbidities and in whom dietary attempts at weight control have been ineffective
• The remission rate for OSA two years after bariatric surgery, related to the amount of weight lost, is 40%

Adjunctive Therapies - Pharmacotherapy and Supplemental Oxygen

• There are no widely effective pharmacotherapies for OSA with the important exceptions of individuals with hypothyroidism or acromegaly
• Treatment of those underlying medical conditions can improve the AHI
• Oxygen supplementation is not recommended as a primary treatment for OSA
• Supplemental oxygen alone may reduce nocturnal hypoxaemia, but may also prolong apnoeas and may potentially worsen hypercapnia in patients with comorbid respiratory disease
• Modafinil is recommended for the treatment of residual excessive daytime sleepiness in OSA patients who have sleepiness despite effective PAP treatment and who are lacking any other identifiable cause of their sleepiness

A Role for Exercise?

• Exercise has been shown to reduce the severity of OSA, independent of BMI
• Exercise has been documented to achieve a 25-30% reduction in OSA severity
• A dietary-induced body mass reduction of 10% is required to achieve this same level of OSA severity improvement
• Even modest improvements in OSA severity have been associated with significantly reduced risk of adverse health outcomes