Screening among family members of people with known FH is cost-effective. Other strategies such as universal screening at the age of 16 were suggested in 2001. The latter approach may however be less cost-effective in the short term. Screening at an age lower than 16 was thought likely to lead to an unacceptably high rate of false positives.

A 2007 meta-analysis found that "the proposed strategy of screening children and parents for familial hypercholesterolaemia could have considerable impact in preventing the medical consequences of this disorder in two generations simultaneously." "The use of total cholesterol alone may best discriminate between people with and without FH between the ages of 1 to 9 years."

Screening of toddlers has been suggested, and results of a trial on 10,000 one-year-olds were published in 2016. Work was needed to find whether screening was cost-effective, and acceptable to families.

Testing the general population under the age of 40 without symptoms is of unclear benefit.

Given the complicated nature of the "clamp" technique (and the potential dangers of hypoglycemia in some patients), alternatives have been sought to simplify the measurement of insulin resistance. The first was the Homeostatic Model Assessment (HOMA), and a more recent method is the Quantitative insulin sensitivity check index (QUICKI). Both employ fasting insulin and glucose levels to calculate insulin resistance, and both correlate reasonably with the results of clamping studies. Wallace "et al." point out that QUICKI is the logarithm of the value from one of the HOMA equations.

Another measure of insulin resistance is the modified insulin suppression test developed by Gerald Reaven at Stanford University. The test correlates well with the euglycemic clamp, with less operator-dependent error. This test has been used to advance the large body of research relating to the metabolic syndrome.

Patients initially receive 25 μg of octreotide (Sandostatin) in 5 mL of normal saline over 3 to 5 minutes via intravenous infusion (IV) as an initial bolus, and then, are infused continuously with an intravenous infusion of somatostatin (0.27 μg/m/min) to suppress endogenous insulin and glucose secretion. Next, insulin and 20% glucose are infused at rates of 32 and 267 mg/m/min, respectively. Blood glucose is checked at zero, 30, 60, 90, and 120 minutes, and thereafter, every 10 minutes for the last half-hour of the test. These last four values are averaged to determine the steady-state plasma glucose level (SSPG). Subjects with an SSPG greater than 150 mg/dL are considered to be insulin-resistant.

Fasting plasma glucose screening should begin at age 30–45 and be repeated at least every three years. Earlier and more frequent screening should be conducted in at-risk individuals. The risk factors for which are listed below:

- Family history (parent or sibling)

- Dyslipidemia (triglycerides > 200 or HDL < 35)

- Overweight or obesity (body mass index > 25)

- History of gestational diabetes or infant born with birth weight greater than

- High risk ethnic group

- Hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure > 90 mmHg)

- Prior fasting blood glucose > 99

- Known vascular disease

- Markers of insulin resistance (PCOS, acanthosis nigricans)

The American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) have developed "lifestyle intervention" guidelines for preventing the onset of type 2 diabetes:

- Healthy meals (a diet with no saturated and trans fats, sugars, and refined carbohydrates, as well as limited the intake of sodium and total calories)

- Physical exercise (30–45 minutes of cardio vascular exercise per day, five days a week)

- Reducing weight by as little as 5–10 percent may have a significant impact on overall health

Testing the general population under the age of 40 without symptoms is of unclear benefit.

Approximately 85% of individuals with this disorder have not been diagnosed and consequently are not receiving lipid-lowering treatments. Physical examination findings can help a physician make the diagnosis of FH. Tendon xanthomas are seen in 20-40% of individuals with FH and are pathognomonic for the condition. A xanthelasma or corneal arcus may also be seen. These common signs are supportive of the diagnosis, but are non-specific findings.

The World Health Organization 1999 criteria require the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following:

- Blood pressure: ≥ 140/90 mmHg

- Dyslipidemia: triglycerides (TG): ≥ 1.695 mmol/L and high-density lipoprotein cholesterol (HDL-C) ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female)

- Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or body mass index > 30 kg/m

- Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g

The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following:

- Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female)

- Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia

- Hypertension: blood pressure ≥ 140/90 mmHg or antihypertensive medication

- Fasting plasma glucose ≥ 6.1 mmol/L

This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma, and premature cardiovascular disease. The incidence of this disease is about one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.

HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in the blood due to the lack of uptake (no Apo B receptors) of LDL particles. This pathology, however, is the second-most common disorder of the various hyperlipoproteinemias, with individuals with a heterozygotic predisposition of one in every 500 and individuals with homozygotic predisposition of one in every million. These individuals may present with a unique set of physical characteristics such as xanthelasmas (yellow deposits of fat underneath the skin often presenting in the nasal portion of the eye), tendon and tuberous xanthomas, arcus juvenilis (the graying of the eye often characterized in older individuals), arterial bruits, claudication, and of course atherosclerosis. Laboratory findings for these individuals are significant for total serum cholesterol levels two to three times greater than normal, as well as increased LDL cholesterol, but their triglycerides and VLDL values fall in the normal ranges. To manage persons with HLPIIa, drastic measures may need to be taken, especially if their HDL cholesterol levels are less than 30 mg/dL and their LDL levels are greater than 160 mg/dL. A proper diet for these individuals requires a decrease in total fat to less than 30% of total calories with a ratio of monounsaturated:polyunsaturated:saturated fat of 1:1:1. Cholesterol should be reduced to less than 300 mg/day, thus the avoidance of animal products and to increase fiber intake to more than 20 g/day with 6g of soluble fiber/day. Exercise should be promoted, as it can increase HDL. The overall prognosis for these individuals is in the worst-case scenario if uncontrolled and untreated individuals may die before the age of 20, but if one seeks a prudent diet with correct medical intervention, the individual may see an increased incidence of xanthomas with each decade, and Achilles tendinitis and accelerated atherosclerosis will occur.

Diagnosis can be made by checking fasting and post prandial insulin levels either with normal meal or with 100gms of oral glucose

Treatment is typically achieved via diet and exercise, although metformin may be used to reduce insulin levels in some patients (typically where obesity is present). A referral to a dietician is beneficial. Another method used to lower excessively high insulin levels is cinnamon as was demonstrated when supplemented in clinical human trials.

A low carbohydrate diet is particularly effective in reducing hyperinsulinism.

A healthy diet that is low in simple sugars and processed carbohydrates, and high in fiber, and vegetable protein is often recommended. This includes replacing white bread with whole-grain bread, reducing intake of foods composed primarily of starch such as potatoes, and increasing intake of legumes and green vegetables, particularly soy.

Regular monitoring of weight, blood sugar, and insulin are advised, as hyperinsulinemia may develop into diabetes mellitus type 2.

It has been shown in many studies that physical exercise improves insulin sensitivity. The mechanism of exercise on improving insulin sensitivity is not well understood however it is thought that exercise causes the glucose receptor GLUT4 to translocate to the membrane. As more GLUT4 receptors are present on the membrane more glucose is taken up into cells decreasing blood glucose levels which then causes decreased insulin secretion and some alleviation of hyperinsulinemia. Another proposed mechanism of improved insulin sensitivity by exercise is through AMPK activity. The beneficial effect of exercise on hyperinsulinemia was shown in a study by Solomon et al. (2009), where they found that improving fitness through exercise significantly decreases blood insulin concentrations.

Vitamin E supplements have shown to help children with the deficiency.

Physicians and basic researchers classify dyslipidemias in two distinct ways:

- Presentation in the body (including the specific type of lipid that is increased)

- Underlying cause for the condition (genetic, or secondary to another condition). This classification can be problematic, because most conditions involve the intersection of genetics and lifestyle issues. However, there are a few well-defined genetic conditions that are usually easy to identify.

Fredrickson Classification:

There are various ways of measuring abdominal obesity including:

- Absolute waist circumference (> in men and > in women)

- Waist–hip ratio (the circumference of the waist divided by that of the hips of >0.9 for men and >0.85 for women)

- Waist-to-height ratio

- Sagittal Abdominal Diameter

In those with a BMI under 35, intra-abdominal body fat is related to negative health outcomes independent of total body fat. Intra-abdominal or visceral fat has a particularly strong correlation with cardiovascular disease.

BMI and waist measurements are well recognized ways to characterize obesity. However, waist measurements are not as accurate as BMI measurements. For this reason, it is recommended to use both methods of measurements.

While central obesity can be obvious just by looking at the naked body (see the picture), the severity of central obesity is determined by taking waist and hip measurements. The absolute waist circumference in men and in women) and the waist-hip ratio (>0.9 for men and >0.85 for women) are both used as measures of central obesity. A differential diagnosis includes distinguishing central obesity from ascites and intestinal bloating. In the cohort of 15,000 people participating in the National Health and Nutrition Examination Survey (NHANES III), waist circumference explained obesity-related health risk better than the body mass index (or BMI) when metabolic syndrome was taken as an outcome measure and this difference was statistically significant. In other words, excessive waist circumference appears to be more of a risk factor for metabolic syndrome than BMI. Another measure of central obesity which has shown superiority to BMI in predicting cardiovascular disease risk is the Index of Central Obesity (waist-to-height ratio - WHtR), where a ratio of >=0.5 (i.e. a waist circumference at least half of the individual's height) is predictive of increased risk.

Another diagnosis of obesity is the analysis of intra-abdominal fat having the most risk to one's personal health. The increased amount of fat in this region relates to the higher levels of plasma lipid and lipoproteins as per studies mentioned by Eric Poehlman (1998) review.

An increasing acceptance of the importance of central obesity within the medical profession as an indicator of health risk has led to new developments in obesity diagnosis such as the Body Volume Index, which measures central obesity by measuring a person's body shape and their weight distribution. The effect of abdominal adiposity occurs not just in those who are obese, but also affects people who are non-obese and it also contributes to insulin sensitivity

In the setting of critical illness, low cholesterol levels are predictive of clinical deterioration, and are correlated with altered cytokine levels.

In humans with genetic loss-of-function variants in one copy of the "ANGPTL3" gene, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of "ANGPTL3", low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").

Hooft disease is a rare condition evidenced by low blood lipid level, red rash and mental and physical retardation.

Index of Central Obesity (ICO) is the ratio of waist circumference and height first proposed by a Parikh "et al." in 2007 as a better substitute to the widely used waist circumference in defining metabolic syndrome. The National Cholesterol Education Program Adult Treatment Panel III suggested cut off of and for males and females as a marker of central obesity. The same was used in defining metabolic syndrome. Misra et al. suggested that these cutoffs are not applicable among Indians and the cutoffs be lowered to and for males and females. Various race specific cutoffs were suggested by different groups. The International Diabetes Federation defined central obesity based on these various race and gender specific cutoffs. The other limitation of waist circumference is that it can not be applied in children.

Parikh et al. looked at the average heights of various races and suggested that by using ICO various race- and gender-specific cutoffs of waist circumference can be discarded. An ICO cutoff of 0.5 was suggested as a criterion to define central obesity. Parikh "et al." further tested a modified definition of metabolic syndrome in which waist circumference was replaced with ICO in the National Health and Nutrition Examination Survey (NHANES) database and found the modified definition to be more specific and sensitive.

This parameter has been used in the study of metabolic syndrome and cardiovascular disease.

Dunnigan-type familial partial lipodystrophy, also known as FPLD Type II and abbreviated as (FPLD2), is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes usually type 2, dyslipidemia, hypertension, and early endpoints of atherosclerosis. It can also result in hepatic steatosis. FPLD results from mutations in LMNA gene, which is the gene that encodes nuclear lamins A and C.

Many drug candidates are in advanced clinical studies as : elafibranor, obeticholic acid.

Pediatric nonalcoholic fatty liver disease (NAFLD) was first reported in 1983. It is currently the primary form of liver disease among children. NAFLD has been associated with the metabolic syndrome, which is a cluster of risk factors that contribute to the development of cardiovascular disease and type 2 diabetes mellitus. Studies have demonstrated that abdominal obesity and insulin-resistance in particular are thought to be key contributors to the development of NAFLD. Because obesity is becoming an increasingly common problem worldwide, the prevalence of NAFLD has been increasing concurrently. Moreover, boys are more likely to be diagnosed with NAFLD than girls with a ratio of 2:1. Studies have suggested that progression toward a more advance stage of disease among children is dependent on age and presence of obesity. This finding is consistent with previous studies in adults demonstrating the same association between age and obesity, and liver fibrosis. Early diagnosis of NAFLD in children may help prevent the development of liver disease during adulthood.

This is challenging as most children with NAFLD are asymptomatic with few showing abdominal pain. Currently, liver biopsy is considered the gold standard for diagnosing NAFLD. However, this method is invasive, costly and bears greater risk for children, and noninvasive screening and diagnosing methods would have significant public health implications for children with NAFLD.

The only treatment shown to be truly effective in childhood NAFLD is weight loss.

Upon suspicion of PAD, the first-line study is the ankle–brachial index (ABI). When the blood pressure readings in the ankles is lower than that in the arms, blockages in the arteries which provide blood from the heart to the ankle are suspected. Normal ABI range of 1.00 to 1.40.The patient is diagnosed with PAD when the ABI is ≤ 0.90 . ABI values of 0.91 to 0.99 are considered "borderline" and values >1.40 indicate noncompressible arteries. PAD is graded as mild to moderate if the ABI is between 0.41 and 0.90, and an ABI less than 0.40 is suggestive of severe PAD. These relative categories have prognostic value.

In people with suspected PAD but normal resting ABIs, exercise testing of ABI can be done. A base line ABI is obtained prior to exercise. The patient is then asked to exercise (usually patients are made to walk on a treadmill at a constant speed) until claudication pain occurs (or a maximum of 5 minutes), following which the ankle pressure is again measured. A decrease in ABI of 15%-20% would be diagnostic of PAD.

It is possible for conditions which stiffen the vessel walls (such as calcifications that occur in the setting of long term diabetes) to produce false negatives usually, but not always, indicated by abnormally high ABIs (> 1.40). Such results and suspicions merit further investigation and higher level studies.

If ABIs are abnormal the next step is generally a lower limb doppler ultrasound examination to look at site and extent of atherosclerosis. Other imaging can be performed by angiography, where a catheter is inserted into the common femoral artery and selectively guided to the artery in question. While injecting a radiodense contrast agent an X-ray is taken. Any flow limiting stenoses found in the x-ray can be identified and treated by atherectomy, angioplasty or stenting. Contrast angiography is the most readily available and widely used imaging technique.

Modern multislice computerized tomography (CT) scanners provide direct imaging of the arterial system as an alternative to angiography.

Magnetic resonance angiography (MRA) is a noninvasive diagnostic procedure that uses a combination of a large magnet, radio frequencies, and a computer to produce detailed images to provide pictures of blood vessels inside the body. The advantages of MRA include its safety and ability to provide high-resolution three-dimensional (3D) imaging of the entire abdomen, pelvis and lower extremities in one sitting.

It is not clear if screening for disease is useful as it has not been properly studied.

Most individuals are asymptomatic and are usually discovered incidentally because of abnormal liver function tests or hepatomegaly noted in unrelated medical conditions. Elevated liver biochemistry is found in 50% of patients with simple steatosis. The serum alanine transaminase level usually is greater than the aspartate transaminase level in the nonalcoholic variant and the opposite in alcoholic FLD (AST:ALT more than 2:1).

Imaging studies are often obtained during the evaluation process. Ultrasonography reveals a "bright" liver with increased echogenicity. Medical imaging can aid in diagnosis of fatty liver; fatty livers have lower density than spleens on computed tomography (CT), and fat appears bright in T1-weighted magnetic resonance images (MRIs). No medical imagery, however, is able to distinguish simple steatosis from advanced NASH. Histological diagnosis by liver biopsy is sought when assessment of severity is indicated.

The treatment of fatty liver depends on its cause, and, in general, treating the underlying cause will reverse the process of steatosis if implemented at an early stage. Two known causes of fatty liver disease are an excess consumption of alcohol and a prolonged diet containing foods with a high proportion of calories coming from lipids. For the patients with non-alcoholic fatty liver disease with pure steatosis and no evidence of inflammation, a gradual weight loss is often the only recommendation. In more serious cases, medications that decrease insulin resistance, hyperlipidemia, and those that induce weight loss have been shown to improve liver function.

For advanced patients with non-alcoholic steatohepatitis (NASH), there are no currently available therapies.

Up to 10% of people with cirrhotic alcoholic FLD will develop hepatocellular carcinoma. The overall incidence of liver cancer in nonalcoholic FLD has not yet been quantified, but the association is well-established.

Bariatric surgery, while not currently recommended as a treatment for fatty liver disease (FLD) alone, has been shown to revert FLD and advanced steatohepatitis in over 90% of people who have undergone this surgery for the treatment of obesity.