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Diabetes Clinical Case Series, Excerpt #11, Endocrinology and Diabetes, The Basics, Part 3

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Lipid abnormalities
  • The two main lipid molecules in the plasma are triglycerides and cholesterol
  • To make these lipid particles water-soluble, they are bound to phospholipids and lipoproteins in plasma
  • Lipid measurements are best performed on a fasting sample. The following measurements can be done:
    • Total cholesterol (TC) high levels are atherogenic. TC is composed of low-density lipoprotein cholesterol (LDLc) – high levels are associated with increased risk of vascular disease – and high-density lipoprotein cholesterol (HDLc) – low levels are associated with increased risk of vascular disease, whereas high levels are protective
    • Triglycerides: high levels are atherogenic and can also result in pancreatitis….

Hyperlipidemia

There are a number of different types of hyperlipidemias, including:

  • Isolated raised cholesterol
    • Polygenic hypercholesterolemia: probably the commonest cause of isolated hypercholesterolemia
    • Familial hypercholesterolemia: an autosomal dominant condition affecting 1:500 people
  • Isolated raised triglycerides
    • Autosomal dominant affecting around 1:300 people, characterized by eruptive xanthomas and pancreatitis
  • Raised cholesterol and triglycerides
    • Familial combined hyperlipidemia: occurs in 1:250 people
  • Secondary causes of hyperlipidemia
    • Diet excessive in fat
    • Diabetes mellitus: mainly affects triglyceride levels (increase) and HDL levels (decrease), particularly in those with poor glucose control
    • Hypothyroidism: affects LDL levels (increase)
    • Renal failure: affects LDL levels (increase), HDL (decrease) and triglycerides (increase)
    • Liver disease: obstructive liver lesions affect LDL levels (increase)
    • Drugs: a number of drugs can affect lipid levels including β-blockers, thiazide diuretics, steroids, protease inhibitors and alcohol
Clinical presentation
  • Patients may be asymptomatic and hyperlipidemia is picked up during routine testing
  • Others can present with complications of hyperlipidemia including:
    • Atherothrombotic disease (myocardial infarction, stroke)
    • Pancreatitis
  • Individuals with secondary hyperlipidemia present with symptoms of original disease
Treatment
  • Lifestyle changes are important (diet, exercise and stopping smoking) as these simple measures can lower LDL and increased HDL levels
  • For primary prevention (individuals with no previous complications due to hyperlipidemia): there are special risk factor engines that calculate future cardiovascular risk and hyperlipidemic agents are usually used in those with more than 20% risk over a 10-year period
  • Individuals with a previous vascular event or high-risk subjects (for example diabetics), are treated with hyperlipidemic agents even in the presence of normal lipid profile
  • Agents used include statins, such as simvastatin, atorvastatin and rosuvastatin
    • Most widely used hyperlipidemic agents due to their undoubted clinical benefits
    • Mode of action is related to decreased synthesis of cholesterol in the liver [inhibition of 3-hydroxy, 3-methylglutaryl coenzyme A (HMG CoA)]
    • Effective at reducing LDL levels, minor effect on HDL and triglycerides
    • Side effects are rare and include muscular aches and pains, derangement in liver function and rhabdomyolysis, a potentially life-threatening complication but fortunately very rare
    • All diabetes patients above the age of 40 are prescribed a statin (regardless of cholesterol levels), to reduce the risk of future vascular events
  • Ezetimibe
    • This agent reduces cholesterol absorption
    • Effective in combination with a statin but less impressive when used alone
  • Fibrates
    • Effective at reducing triglycerides and, to a lesser extent, LDL levels. Also, they raise HDL levels
    • Their role in reducing cardiovascular risk is not as clear as statins
    • Usually used as second- or third-line treatment, except in those with isolated hypertriglyceridemia, when fibrates are used as first-line treatment
  • Nicotinic acid
    • Very effective at increasing HDL levels
    • The role of this agent in cardiovascular protection is unknown
    • Use is limited by side effects (severe flushing)
  • Omega-3 fatty acids
    • Effective at reducing triglyceride levels
Obesity
  • A major health problem in the developed world and it is on the increase
  • Related largely to increased food intake and sedentary lifestyle
  • Genetic factors play a role as some individuals are more susceptible to developing obesity
  • There are some rare cases of obesity that have a clear genetic basis (monogenic obesity), including:
    • Leptin and leptin receptor deficiency
    • Prader-Willi syndrome
    • Laurence-Moon-Biedl syndrome
  • Complications of obesity include:
    • Insulin resistance and diabetes mellitus
    • Lipid abnormalities
    • Cardiovascular disease
    • Hypertension
    • Mechanical joint pain and osteoarthritis
    • Sleep apnea
    • Increased risk of cancers
    • Reproductive abnormalities (PCOS, impaired fertility)
Clinical presentation
  • Concerns over body image secondary to obesity
  • Complications (e.g. diabetes, cardiovascular disease)

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Investigations
  • Fasting glucose (rule out diabetes)
  • Fasting lipid profile
  • Thyroid function tests
  • ECG
  • Specific tests in case of clinical suspicion (such as Cushing’s syndrome for example)
Treatment
  • Lifestyle changes
    • Diet: it is always useful to arrange an appointment with a dietitian as minor changes in dietary habits can have a major influence on weight reduction
    • Increase exercise activity
  • More severe dietary restrictions: those with severe obesity are sometimes admitted to hospital to initiate a very low calorie diet under clinical supervision
  • Drug treatment
    • Orlistat inhibits gut lipase activity and reduces fat absorption. Patient should comply with low-fat diet. Side effects include diarrhea (oily diarrhea is characteristic), often in those who do not comply with reduction in fat intake
  • Surgery
    • Gastric bypass surgery is an effective treatment but reserved for those with severe obesity who are not responding to lifestyle changes and/or medical treatment

Pharmaceutical Interventions:

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The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports a broad range of basic and clinical obesity research. More information about obesity research is available at http://www.obesityresearch.nih.gov

Ramzi Ajjan, MRCP, Med Sci, PhD, Senior Lecturer and Honorary Consultant in Diabetes and Endocrinology, Department of Health Clinician Scientist, The LIGHT Laboratories, University of Leeds, Leeds, UK
 

A John Wiley & Sons, Ltd., Publication This edition first published 2011 © 2011 by John Wiley & Sons, Ltd.

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