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Hypertriglyceridemia

In medicine, hypertriglyceridemia (or "Hypertriglyceridaemia") denotes high

(hyper-) blood levels (-emia) of triglycerides, the most abundant fatty molecule in

most organisms. It has been associated with atherosclerosis, even in the absence of

hypercholesterolemia (high cholesterol levels). It can also lead to pancreatitis in

excessive concentrations. Very high triglyceride levels may also interfere with

blood tests; hyponatremia may be reported spuriously (pseudohyponatremia).

Signs and symptoms

Modestly elevated triglyceride levels do not lead to any physical symptoms. Higher levels are

associated with lipemia retinalis (white appearance of the retina), eruptive xanthomas (small

lumps in the skin, sometimes itchy).

Causes

y Idiopathic (constitutional)

y Obesityy High carbohydrate diet

y Diabetes mellitus and insulin resistance - it is one of the defined components of metabolicsyndrome (along with central obesity, hypertension, and hyperglycemia)

y Excess alcohol intakey Nephrotic syndrome

y Genetic predispositiony Certain medications (e.g., isotretinoin)

y Hypothyroidism (underactive thyroid)

Treatment

Treatment of hypertriglyceridemia is by restriction of carbohydrates and fat in the diet, as well as

with niacin, fibrates and statins (three classes of drugs). Increased fish oil intake maysubstantially lower an individual's triglycerides.

[1][2][3]

Clinical practice guidelines by the National Cholesterol Education Program (NCEP) suggests

that pharmacotherapy be considered with a triglycerides level over 200 mg/dL.[4] The guidelinesstate "the sum of LDL + VLDL cholesterol (termed non-HDL cholesterol [total cholesterol -

HDL cholesterol]) as a secondary target of therapy in persons with high triglycerides (200mg/dL). The goal for non-HDL cholesterol in persons with high serum triglycerides can be set at

30 mg/dL higher than that for LDL cholesterol (Table 9) on the premise that a VLDL cholesterollevel 30 mg/dL is normal."

[4]

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NonHDL cholesterol contains the highly atherogenic, small, dense lipoproteins that areassociated with a high incidence of cardiovascular disease (CVD). Studies subsequent to the

NCEP report have shown that the nonHDL cholesterol level predicts CVD in people who havediabetes. It may be superior to LDL cholesterol in this regard, and should be used as the primary

lipid target in persons with diabetes.[5]

Primary prevention

Omega-3 fatty acid supplementation in the form of fish oil has been found to be effective indecreasing levels of triglycerides and thus all cardiovascular events by 19% to 45%.[6]

Gemfibrozil twice daily in asymptomatic men ages 4055 without heart disease was also found

to be effective at reducing cardiac endpoints at 5 years (4.14% to 2.73%). This means that 54people must take the treatment for five years to prevent one cardiac event (number needed to

treat of 54).[7]

Secondary prevention

A randomized controlled trial of men with known heart disease and HDL cholesterol of 40 mg/dl

or less , 600 mg of gemfibrozil twice daily reduced cardiac endpoints (non-fatal myocardialinfarction or death from coronary causes) at 5 years from 21.7% to 17.3%. This means that 23

patients must be treated for five years to prevent one cardiac event (number needed to treat is23).

[8]

Familial hypertriglyceridemia

Familial hypertriglyceridemia is a common disorder passed down through families

in which the level of triglycerides (a type of fat) in a person's blood are higher than

normal.

The condition is not associated with a significant increase in cholesterol levels.

Causes

Familial hypertriglyceridemia is caused by a genetic defect, which is passed on inan autosomal dominant fashion. This means that if you get a bad copy of the gene

from just one of your parents, you will have the condition.

Some people with this condition also have high levels of very low density

lipoprotein (VLDL). The reason for the rise in triglycerides and VLDL is not

understood.

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Familial hypertriglyceridemia does not usually become noticeable until puberty or

early adulthood. Obesity, hyperglycemia (high blood glucose levels), and high

levels of insulin are frequently associated with this condition and make cause even

higher triglyceride levels.

Familial hypertriglyceridemia occurs in about 1 in 500 individuals in the United

States. Risk factors are a family history of hypertriglyceridemia or a family history

of heart disease before the age of 50.

Symptoms

You may not notice any symptoms. People with the condition may have coronary

artery disease at an early age.

Exams and Tests

People with a family history of this condition should have blood tests to check very

low density lipoprotein (VLDL) and triglyceride levels. Blood tests usually show a

mild to moderate increase in triglycerides.

A coronary risk profile may also be done.

Treatment

The goal of treatment is to control conditions that can raise triglyceride levels suchas obesity, hypothyroidism, and diabetes.

Your doctor may tell you not to drink alcohol. Because certain birth control pills

can raise triglyceride levels, you should carefully discuss their use with your

doctor.

Treatment also involves avoiding excess calories and foods high in saturated fats

and carbohydrates.

If high triglyceride levels persist despite diet changes, medication may be needed.Nicotinic acid and gemfibrozil have been shown to lower triglyceride levels in

people with this condition.

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Outlook(Prognosis)

Persons with this condition have an increased risk of coronary artery disease and

pancreatitis.

Losing weight and keeping diabetes under control helps improve the outcome.

Possible Complications

y Pancreatitisy Coronary artery disease

PreventionScreening family members for high triglycerides may detect the disease early.

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High-density lipoprotein

High-density lipoprotein (HDL) is one of the five major groups of lipoproteins

(chylomicrons, VLDL, IDL, LDL, HDL) that enable lipids like cholesterol andtriglycerides to be transported within the water-based bloodstream. In healthy

individuals, about thirty percent of blood cholesterol is carried by HDL.[1]

It is hypothesized that HDL can remove cholesterol from atheroma within arteries

and transport it back to the liver for excretion or re-utilization, which is the main

reason why HDL-bound cholesterol is sometimes called "good cholesterol", or

HDL-C. A high level of HDL-C seems to protect against cardiovascular diseases,

and low HDL cholesterol levels (less than 40 mg/dL or about 1mmol/L) increase

the risk for heart disease. Cholesterol contained in HDL particles is considered

beneficial for the cardiovascular health, in contrast to "bad" LDL cholesterol.

Structure and function

HDL is the smallest of the lipoprotein particles. They are the densest because they

contain the highest proportion of protein. Their most abundant apolipoproteins are

apo A-I and apo A-II.[2]

The liver synthesizes these lipoproteins as complexes of

apolipoproteins and phospholipid, which resemble cholesterol-free flattened

spherical lipoprotein particles. They are capable of picking up cholesterol, carried

internally, from cells by interaction with the ATP-binding cassette transporter A1(ABCA1). A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT)

converts the free cholesterol into cholesteryl ester (a more hydrophobic form of

cholesterol), which is then sequestered into the core of the lipoprotein particle,

eventually making the newly synthesized HDL spherical. They increase in size as

they circulate through the bloodstream and incorporate more cholesterol and

phospholipid molecules from cells and other lipoproteins, for example by the

interaction with the ABCG1 transporter and the phospholipid transport protein

(PLTP).

HDL transports cholesterol mostly to the liver or steroidogenic organs such asadrenals, ovary, and testes by direct and indirect pathways. HDL is removed by

HDL receptors such as scavenger receptor BI (SR-BI), which mediate the selective

uptake of cholesterol from HDL. In humans, probably the most relevant pathway is

the indirect one, which is mediated by cholesteryl ester transfer protein (CETP).

This protein exchanges triglycerides of VLDL against cholesteryl esters of HDL.

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As the result, VLDLs are processed to LDL, which are removed from the

circulation by the LDL receptor pathway. The triglycerides are not stable in HDL,

but degraded by hepatic lipase so that finally small HDL particles are left, which

restart the uptake of cholesterol from cells.

The cholesterol delivered to the liver is excreted into the bile and, hence, intestine

either directly or indirectly after conversion into bile acids. Delivery of HDL

cholesterol to adrenals, ovaries, and testes is important for the synthesis of steroid

hormones.

Several steps in the metabolism of HDL can contribute to the transport of

cholesterol from lipid-laden macrophages of atherosclerotic arteries, termed foam

cells, to the liver for secretion into the bile. This pathway has been termed reverse

cholesterol transportand is considered as the classical protective function of HDL

toward atherosclerosis.

However, HDL carries many lipid and protein species, several of which have very

low concentrations but are biologically very active. For example, HDL and their

protein and lipid constituents help to inhibit oxidation, inflammation, activation of

the endothelium, coagulation, and platelet aggregation. All these properties maycontribute to the ability of HDL to protect from atherosclerosis, and it is not yet

known what are the most important.

Recommended range

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The American Heart Association, NIH and NCEP provides a set of guidelines for fasting HDLlevels and risk for heart disease.

Level mg/dLLevelmmol/L

Interpretation

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y One drink of alcohol a day or less yields higher HDL-B levels, more so in women thanmen. HDL transports cholesterol to the liver and cholesterol is known to have a

protective effect on the cell membrane. It is likely that this reflects the liver's need formore cholesterol to protect itself from the alcohol.

y

Adding soluble fiber to diety Using supplements such as omega 3 fish oil or flax oily Increasing intake ofcis-unsaturated fats and cholesterol, decreasing intake oftrans-fats.

y Avoiding supplements that contain omega 6 fish oil (omega 6 reduces cholesterol butdoes not discriminate between good and bad cholesterol) as well as limiting foods high in

omega 6 (tilapia, most vegetable oils, nuts)

A very-low-carbohydrate diet involving ketogenesis may have similar response to taking niacinas described above (lowered LDL and increased HDL) through beta-hydroxybutyrate coupling

the Niacin receptor 1.

Drugs

Pharmacological therapy to increase the level of HDL cholesterol includes use of fibrates and

niacin. Fibrates, however, have shown that they have no effect on overall deaths from all causes,despite their effects on lipids.

[21]

Niacin (B3), increases HDL by selectively inhibiting hepatic Diacylglycerol acyltransferase 2,

reducing triglyceride synthesis and VLDL secretion through a receptor HM74[22] otherwise

known as Niacin receptor 2 and HM74A / GPR109A,[20]

Niacin receptor 1.

Pharmacologic (1- to 3-gram) doses increase HDL levels by 1030%, making it the most

powerful agent to increase HDL-cholesterol. A randomized clinical trial demonstrated thattreatment with niacin can significantly reduce atherosclerosis progression and cardiovascular

events.[26] However, niacin products sold as "no-flush", i.e. not having side-effects such as"niacin flush", do not contain free nicotinic acid and are therefore ineffective at raising HDL,

while products sold as "sustained-release" may contain free nicotinic acid, but "some brands arehepatotoxic"; therefore the recommended form of niacin for raising HDL is the cheapest,

immediate-release preparation. Both fibrates and niacin increase artery toxic homocysteine, aneffect that can be counteracted by also consuming a multivitamin with relatively high amounts of

the B-vitamins. Pharmacologic (1- to 3-gram) doses increase HDL levels by 1030%, making itthe most powerful agent to increase HDL-cholesterol. A randomized clinical trial demonstrated

that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular

events. However, niacin products sold as "no-flush", i.e. not having side-effects such as "niacinflush", do not contain free nicotinic acid and are therefore ineffective at raising HDL, whileproducts sold as "sustained-release" may contain free nicotinic acid, but "some brands are

hepatotoxic"; therefore the recommended form of niacin for raising HDL is the cheapest,immediate-release preparation.

In contrast, while the use of statins is effective against high levels of LDL cholesterol, it has littleor no effect in raising HDL cholesterol.

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DIABETICCATARACT

While diabetes induced cataracts is common in older people, those with diabetesare more susceptible to experiencing problems at a younger age. People who have

diabetes are at a higher risk of losing clear vision due to the faster progression of

the disease.

Diabetes induced cataracts clouds the lens of the eyes blocking light, which results

in bleared vision. Left untreated diabetes induced cataracts can seriously limit a

diabetics vision, allowing a person to only see light and dark images.

Mild diabetes induced cataracts, at times, can be treated with prescription

eyeglasses. If diabetes induced cataracts is left undiagnosed over time the cataractscan impair a persons lifestyle. People who suffer from cataracts often find

themselves having to give up driving. Vision has become cloudy and it is near

impossible for them to distinguish road sign or streetlights. Diabetics, like other

people with cataracts reach a point when they are even unable to distinguish a

pedestrian crossing the street.

Those who do suffer from cataracts and who have avoided getting treatment find

that their entire lifestyle is turned upside down. Before they know it, their

independence is lost and they are, know longer able to live alone.

As for the question of how to deal with diabetes induced cataracts, there are very

limited options. Natural supplements have been proven to help or there is the

surgically option. Yet if the diabetes is too far out of control, and the blood sugar

is too high, the surgical option no longer applies.

Blood sugar levels play an important roll between the diabetic and their eyesight.

The lower the blood sugar is maintained the greater the chance of keeping the

formation of cataracts at bay. One-way to deal with cataracts for the diabetic is to

have your eyes checked regularly, keep blood sugar under control, and do notignore any symptom that might be considered a warning sign of eye problems

developing. Diabetic should have their eyes checked once a year, this way if

diabetes induced cataracts has started treatment can get started immediately.

It is surprising to know that many medications that a diabetic or anyone else takes

can have drastic effects on ones eyes, medications for heart disease and depression

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can have adverse effects on ones eyes, causing everything from glaucoma to

retinopathy, to cataracts to eventual blindness. Knowing this you may fear taking

medications and fear having a surgical procedure.

Diabetic cataract: rare, usually bilateral, opacity shaped like a snowflake,affecting the anterior and posterior cortices of young diabetics; sometimesit can be reversed when the blood glucose is brought under control, but inmost cases it progresses rapidly to a mature cataract.

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Cardiovascular Autonomic Neuropathy Due to

Diabetes Mellitus:

CAN is a common form of diabetic autonomic

neuropathy and causes

abnormalities in heart rate control aswell as central and peripheral vascular

dynamics. The clinical

manifestations of CAN include exercise intolerance,

intraoperative

cardiovascular lability, orthostatic hypotension, painless

myocardial

ischemia, and increased risk of mortality. CAN contributes to

morbidity, mortality, and reduced quality of life for personswith diabetes

THE AUTONOMIC NERVOUS system modulates the electrical and contractile

activity of the myocardium via the interplay of sympatheticand parasympathetic

activity. An imbalance of autonomiccontrol is implicated in the pathophysiology

of arrhythmogenesis. Cardiovascular autonomic neuropathy (CAN), a common

formof autonomic dysfunction found in patients with diabetes mellitus,

causes

abnormalities in heart rate control, as well as defectsin central and peripheral

vascular dynamics. Individuals withparasympathetic dysfunction have a high

resting heart rate most

likely because of vagal neuropathy that results in

unopposed

increased sympathetic outflow. Persons with a combined

parasympathetic/sympathetic

dysfunction have slower heart rates. With

advanced nerve dysfunction,heart rate is fixed. Thus, it is apparent that the

determination

of heart rate itself is not a reliable diagnostic sign of CAN.

Reduction in variability of heart rate is the earliest indicatorof CAN. Clinical

manifestations ofCAN include exercise intolerance,intraoperative cardiovascular

lability, orthostatic hypotension

(OH), asymptomatic ischemia, painless

myocardial infarction

(MI), and increased risk of mortality

Exercise intolerance

In diabetic individuals with CAN, exercise tolerance is limitedas a result of

impaired parasympathetic/sympathetic responsesthat would normally enhance

cardiac output and result in directing peripheral blood flow to skeletal muscles.

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Reduced ejectionfraction, systolic dysfunction, and decreased diastolic filling,

potentially as a result ofCAN, also limit exercise tolerance. For diabetic persons

likely to have CAN, it has been suggestedthat cardiac stress testing should be

performed before beginning

an exercise program. When discussing exercise

instructions

and goals with patients with CAN, healthcare providers need

to

emphasize that the use of heart rate is an inappropriate gauge of exercise intensity

because maximal heart rate is depressedin persons with CAN. Recently it has been

shown that percentageof heart rate reserve, an accurate predictor of percentage of

VO2 reserve, can be used to prescribe and monitor exercise intensityin diabetic

individuals with CAN

Intraoperative cardiovascular lability

There is a 2- to 3-fold increase in cardiovascular morbidity

and mortality

intraoperatively for patients with diabetes.

Studies have demonstrated that theinduction of anesthesia causes

a greater degree of decline in heart rate and blood

pressurein diabetic patients compared with nondiabetic individuals and that

hemodynamic stability, in the intraoperative period,depends on the severity of

autonomic dysfunction. Patientswith severe autonomic dysfunction have a high

risk of blood pressure instability, and intraoperative blood pressure

support is

needed more often in those with greater impairment. Intraoperative hypothermia,

which may decrease drugmetabolism and affect wound healing, and impaired

hypoxic-inducedventilatory drive have also been shown to be associated

with the

presence ofCAN.

Orthostatic hypotension

A change from lying to standing normally results in activationof a baroreceptor-

initiated, centrally mediated sympathetic

reflex, resulting in an increase in

peripheral vascular resistanceand cardiac acceleration. OH is characterized by a

defectin this reflex arc, resulting in signs and symptoms such as

weakness,

faintness, dizziness, visual impairment, and syncope.Although the absolute fall in

blood pressure is arbitrary, OHis usually defined as a fall in blood pressure [i.e.

>2030mm Hg for systolic or >10 mm Hg for diastolic in

response to postural

change, from supine to standing.

Painless myocardial ischemia

Inability to detect ischemic pain can impair the recognitionof myocardial ischemia

orMI. The mechanisms of painless myocardialischemia are, however, complex

and not fully understood. Altered pain thresholds, subthreshold ischemia not

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sufficient to inducepain, and dysfunction of the afferent cardiac autonomic nerve

fibers have all been suggested as possible mechanisms

Increased risk of mortality

Impaired autonomic control of heart rate is linked to increased risk of mortality.Reduced parasympathetic function or increased

sympathetic activity may provide

the propensity for lethal arrhythmias

Treatment Interventions to Ameliorate Cardiovascular

Autonomic Dysfunction via Pharmacological Agents

Glycemic control

For persons with type 2 diabetes, intensive insulin therapy showed a small

tendency for improved autonomicfunction, whereas deterioration was noted in the

conventionallytreated group

Antioxidants

During chronic hyperglycemia, the metabolism of glucose alsoresults in the

generation of free radicals. Although free radicalsof superoxide and hydrogen

peroxide are essential for normalcell function, excessive accumulation of free

radicals is detrimental

and has a direct neurotoxic effect. -Lipoic acid, anantioxidant

that reduces free radical formation, appears to slow progression

of

CAN. For persons with type 2 diabetes, the improvementin CAN was seen after 4

months of treatment with an oral dosageof 800 mg/d .

Angiotensin converting enzyme (ACE) inhibitors

Microvascular insufficiency has also been proposed as a potentialcomponent in the

pathogenesis of diabetic neuropathy. Resultsof animal studies have suggested that

impaired ganglion blood

flow in diabetes could be responsible for

neurodegenerative

changes in autonomic postganglionic cell bodies

Angiotensin type 1 blockers

Angiotensin type 1 (AT1) receptor mediates all potentially deleteriouseffects of

angiotensin II. AT1 antagonists block the AT1receptor, thus blocking the harmful

effects of angiotensin II.

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Aldosterone blockers

Aldosterone has been shown to affect the autonomic nervous system

with

sympathetic activation and parasympathetic inhibitionand impair the baroreflex

response. Other dysfunctionsassociated with aldosterone include the blockage of

myocardial uptake of norepinephrine in animal models and decreasedarterial and

venous compliance, leading to vascular organ damage. Spironolactone, an

aldosterone-receptor blocker, has beenused to reduce the morbidity and mortality

for patients withsevere heart failure