For treatment of type II, dietary modification is the initial approach, but many patients require treatment with statins (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride level is markedly raised, fibrates (peroxisome proliferator-activated receptor-alpha agonists) may be preferable due to their beneficial effects. Combination treatment of statins and fibrates, while highly effective, causes a markedly increased risk of myopathy and rhabdomyolysis, so is only done under close supervision. Other agents commonly added to statins are ezetimibe, niacin, and bile acid sequestrants. Dietary supplementation with fish oil is also used to reduce elevated triglycerides, with the greatest effect occurring in patients with the greatest severity. Some evidence exists for benefit of plant sterol-containing products and omega-3 fatty acids.

FH is usually treated with statins. Statins act by inhibiting the enzyme hydroxymethylglutaryl CoA reductase (HMG-CoA-reductase) in the liver. In response, the liver produces more LDL receptors, which remove circulating LDL from the blood. Statins effectively lower cholesterol and LDL levels, although sometimes add-on therapy with other drugs is required, such as bile acid sequestrants (cholestyramine or colestipol), nicotinic acid preparations or fibrates. Control of other risk factors for cardiovascular disease is required, as risk remains somewhat elevated even when cholesterol levels are controlled. Professional guidelines recommend that the decision to treat a person with FH with statins should not be based on the usual risk prediction tools (such as those derived from the Framingham Heart Study), as they are likely to underestimate the risk of cardiovascular disease; unlike the rest of the population, FH have had high levels of cholesterol since birth, probably increasing their relative risk. Prior to the introduction of the statins, clofibrate (an older fibrate that often caused gallstones), probucol (especially in large xanthomas) and thyroxine were used to reduce LDL cholesterol levels.

More controversial is the addition of ezetimibe, which inhibits cholesterol absorption in the gut. While it reduces LDL cholesterol, it does not appear to improve a marker of atherosclerosis called the intima-media thickness. Whether this means that ezetimibe is of no overall benefit in FH is unknown.

There are no interventional studies that directly show mortality benefit of cholesterol lowering in FH. Rather, evidence of benefit is derived from a number of trials conducted in people who have polygenic hypercholesterolemia (in which heredity plays a smaller role). Still, a 1999 observational study of a large British registry showed that mortality in people with FH had started to improve in the early 1990s when statins were introduced.

A cohort study suggested that treatment of FH with statins leads to a 48% reduction in death from coronary heart disease to a point where people are no more likely to die of coronary heart disease than the general population. However, if the person already had coronary heart disease the reduction was 25%. The results emphasize the importance of early identification of FH and treatment with statins.

Alirocumab and evolocumab, both monoclonal antibodies against PCSK9, are specifically indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia, who require additional lowering of LDL cholesterol.

Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.

This form is due to high triglyceride level. Other lipoprotein levels are normal or increased a little.

Treatment include diet control, fibrates and niacins. Statins are not better than fibrates when lowering triglyceride levels.

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.

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

Homozygous FH is harder to treat. The LDL receptors are minimally functional, if at all. Only high doses of statins, often in combination with other medications, are modestly effective in improving lipid levels. If medical therapy is not successful at reducing cholesterol levels, LDL apheresis may be used; this filters LDL from the bloodstream in a process reminiscent of dialysis. Very severe cases may be considered for a liver transplant; this provides a liver with normally functional LDL receptors, and leads to rapid improvement of the cholesterol levels, but at the risk of complications from any solid organ transplant (such as rejection, infections, or side-effects of the medication required to suppress rejection). Other surgical techniques include partial ileal bypass surgery, in which part of the small bowel is bypassed to decrease the absorption of nutrients and hence cholesterol, and portacaval shunt surgery, in which the portal vein is connected to the vena cava to allow blood with nutrients from the intestine to bypass the liver.

Lomitapide, an inhibitor of the microsomal triglyceride transfer protein, was approved by the US FDA in December 2012 as an orphan drug for the treatment of homozygous familial hypercholesterolemia. In January 2013, The US FDA also approved mipomersen, which inhibits the action of the gene apolipoprotein B, for the treatment of homozygous familial hypercholesterolemia. Gene therapy is a possible future alternative.

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

Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day), and a healthy, reduced calorie diet. Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily due to a lack of compliance with lifestyle and diet changes. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.

The Caerphilly Heart Disease Study followed 2,375 male subjects over 20 years and suggested the daily intake of a pint (~568 ml) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors' findings, while others dispute them. A systematic review of four randomized controlled trials found that a paleolithic nutritional pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components.

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

The progression to type 2 diabetes mellitus is not inevitable for those with prediabetes. The progression into diabetes mellitus from prediabetes is approximately 25% over three to five years.

The first line treatment is change of lifestyle (e.g., Dietary Guidelines for Americans and physical activity). However, if in three to six months of efforts at remedying risk factors prove insufficient, then drug treatment is frequently required. Generally, the individual disorders that compose the metabolic syndrome are treated separately. Diuretics and ACE inhibitors may be used to treat hypertension. Cholesterol drugs may be used to lower LDL cholesterol and triglyceride levels, if they are elevated, and to raise HDL levels if they are low. Use of drugs that decrease insulin resistance, e.g., metformin and thiazolidinediones, is controversial; this treatment is not approved by the U.S. Food and Drug Administration. Weight loss medications may result in weight loss. As obesity is often recognized as the culprit behind many of the additional symptoms, with weight loss and lifestyle changes in diet, physical activity, the need for other medications may diminish.

A 2003 study indicated cardiovascular exercise was therapeutic in approximately 31% of cases. The most probable benefit was to triglyceride levels, with 43% showing improvement; but fasting plasma glucose and insulin resistance of 91% of test subjects did not improve.

Many other studies have supported the value of physical activity and dietary modifications to treat metabolic syndrome. Some natural compounds, like ursolic acid, have been suggested as a treatment for obesity/metabolic syndrome based on the results of extensive research involving animal models; it is argued, however, that there is still a lack of data regarding the use of ursolic acid in humans, as phase-II/III trials of that drug have not been carried so far.

Restricting the overall dietary carbohydrate intake is more effective in reducing the most common symptoms of metabolic syndrome than the more commonly prescribed reduction in dietary fat intake.

The combination preparation simvastatin/sitagliptin (marketed as Juvisync) was introduced in 2011 and the use of this drug was to lower LDL levels and as well as increase insulin levels. This drug could have been used to treat metabolic syndrome but was removed from the market by Merck in 2013 due to business reasons.

High-dose statins, recommended to reduce cardiovascular risk, have been associated with higher progression to diabetes, particularly in patients with metabolic syndrome. The biological mechanisms are not entirely understood, however, the plausible explanation may lie in competitive inhibition of glucose transport via the solute carrier (SLC) family of transporters (specifically "SLCO1B1"), important in statin pharmacokinetics.

Some studies on mice suggest that a Time Restricted Diet (TRD) could be helpful in reversing obesity and possibly metabolic syndrome

Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin levels can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

Since hyperinsulinemia and obesity are so closely linked it is hard to determine whether hyperinsulinemia causes obesity or obesity causes hyperinsulinemia, or both.

Obesity is characterized by an excess of adipose tissue – insulin increases the synthesis of fatty acids from glucose, facilitates the entry of glucose into adipocytes and inhibits breakdown of fat in adipocytes.

On the other hand, adipose tissue is known to secrete various metabolites, hormones and cytokines that may play a role in causing hyperinsulinemia. Specifically cytokines secreted by adipose tissue directly affect the insulin signalling cascade, and thus insulin secretion. Adiponectins are cytokines that are inversely related to percent body fat; that is people with a low body fat will have higher concentrations of adiponectins where as people with high body fat will have lower concentrations of adiponectins. Weyer "et al." (2011) reported that hyperinsulinemia is strongly associated with low adiponectin concentrations in obese people, though whether low adiponectin has a causal role in hyperinsulinemia remains to be established.

- May lead to hypoglycemia or diabetes

- Increased risk of PCOS

- Increased synthesis of VLDL (hypertriglyceridemia)

- Hypertension (insulin increases sodium retention by the renal tubules)

- Coronary Artery Disease (increased insulin damages endothelial cells)

- Increased risk of cardiovascular disease

- Weight gain and lethargy (possibly connected to an underactive thyroid)

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.

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.

The term "non-syndromic obesity" is sometimes used to exclude these conditions. In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.

A permanent routine of exercise, eating healthily, and, during periods of being overweight, consuming the same number or fewer calories than used will prevent and help fight obesity. A single pound of fat yields approximately 3500 calories of energy (32 000 kJ energy per kilogram of fat), and weight loss is achieved by reducing energy intake, or increasing energy expenditure, thus achieving a negative balance. Adjunctive therapies which may be prescribed by a physician are orlistat or sibutramine, although the latter has been associated with increased cardiovascular events and strokes and has been withdrawn from the market in the United States, the UK, the EU, Australia, Canada, Hong Kong, Thailand, Egypt and Mexico.

A 2006 study published in the International Journal of Sport Nutrition and Exercise Metabolism, suggests that combining cardiovascular (aerobic) exercise with resistance training is more effective than cardiovascular training alone in getting rid of abdominal fat. An additional benefit to exercising is that it reduces stress and insulin levels, which reduce the presence of cortisol, a hormone that leads to more belly fat deposits.

Self-motivation by understanding the risks associated with abdominal obesity is widely regarded as being far more important than worries about cosmetics. In addition, understanding the health issues linked with abdominal obesity can help in the self-motivation process of losing the abdominal fat. As mentioned above, abdominal fat is linked with cardiovascular disease, diabetes, and cancer. Specifically it's the deepest layer of belly fat (the fat you cannot see or grab) that poses health risks, as these "visceral" fat cells produce hormones that can affect health (e.g. increased insulin resistance and/or breast cancer risk). The risk increases considering the fact that they are located in the proximity or in between organs in the abdominal cavity. For example, fat next to the liver drains into it, causing a fatty liver, which is a risk factor for insulin resistance, setting the stage for Type 2 diabetes.

In the presence of diabetes mellitus type 2, the physician might instead prescribe metformin and thiazolidinediones (rosiglitazone or pioglitazone) as antidiabetic drugs rather than sulfonylurea derivatives. Thiazolidinediones may cause slight weight gain but decrease "pathologic" abdominal fat (visceral fat), and therefore may be prescribed for diabetics with central obesity.

Thiazolidinedione has been associated with heart failure and increased cardiovascular risk; so it has been withdrawn from the market in Europe by EMA in 2010.

Low-fat diets may not be an effective long-term intervention for obesity: as Bacon and Aphramor wrote, "The majority of individuals regain virtually all of the weight that was lost during treatment." The Women's Health Initiative ("the largest and longest randomized, controlled dietary intervention clinical trial") found that long-term dietary intervention increased the waist circumference of both the intervention group and the control group, though the increase was smaller for the intervention group. The conclusion was that mean weight decreased significantly in the intervention group from baseline to year 1 by 2.2 kg (P<.001) and was 2.2 kg less than the control group change from baseline at year 1. This difference from baseline between control and intervention groups diminished over time, but a significant difference in weight was maintained through year 9, the end of the study.

There are numerous theories as to the exact cause and mechanism in Type 2 Diabetes. Central obesity is known to predispose individuals for insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines that may possibly impair glucose tolerance. But adiponectin which is found in lower concentration in obese and diabetic individuals has shown to be beneficial and protective in Type 2 diabetes mellitus.

Insulin resistance is a major feature of Diabetes Mellitus Type 2 (T2DM), and central obesity is correlated with both insulin resistance and T2DM itself. Increased adiposity (obesity) raises serum resistin levels, which in turn directly correlate to insulin resistance. Studies have also confirmed a direct correlation between resistin levels and T2DM. And it is waistline adipose tissue (central obesity) which seems to be the foremost type of fat deposits contributing to rising levels of serum resistin. Conversely, serum resistin levels have been found to "decline" with decreased adiposity following medical treatment.

Acanthosis nigricans is likely to improve in circumstances where a known cause is removed. For example, obesity-related acanthosis nigricans will improve with weight loss, and drug-induced acanthosis nigricans is likely to resolve when the drug is ceased. Hereditary variants may or may not fade with age, and malignancy-associated variants may, after a malignancy is removed, fade.

Although genetic deficiencies are currently considered rare, variations in these genes may predispose to common obesity. Many candidate genes are highly expressed in the central nervous system.

Several additional loci have been identified. Also, several quantitative trait loci for BMI have been identified.

Confirmed and hypothesized associations include:

Some studies have focused upon inheritance patterns without focusing upon specific genes. One study found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.

The thrifty gene hypothesis postulates that due to dietary scarcity during human evolution people are prone to obesity. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would more likely survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This is the presumed reason that Pima Indians, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.

Numerous studies of laboratory rodents provide strong evidence that genetics plays an important role in obesity.

The risk of obesity is determined by not only specific genotypes but also gene-gene interactions. However, there are still challenges associated with detecting gene-gene interactions for obesity.

In young persons, AN is a visible marker which strongly suggests insulin resistance. Higher than normal insulin levels in the blood stream cause the growth of darkened skin over certain areas of the body. No skin treatment will get rid of AN. Acanthosis nigricans may lighten up and possibly go away by treating the root cause, insulin resistance, but it can take months or years to do so. Insulin resistance syndromes may be divided into type A (HAIR-AN) and type B syndromes.

The majority of cases of acanthosis nigricans are associated with obesity and otherwise idiopathic. This is likely because of insulin resistance, and more likely to occur in darker-skinned persons. This can also be referred to as pseudoacanthosis nigricans.

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

No pharmacological treatment has received approval as of 2015. Some studies suggest diet, exercise, and antiglycemic drugs may alter the course of the disease. General recommendations include improving metabolic risk factors and reducing alcohol intake. While many treatments appear to improve biochemical markers such as alanine transaminase levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints.

Bariatric surgery may also be effective.

Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in people with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients by replacing purine nucleotides and open new avenues of therapeutic intervention. Other non-clinical treatment options include educational programs tailored to their individual needs. Sensorineural hearing loss has been treated with cochlear implantation with good results. Ataxia and visual impairment from optic atrophy are treated in a routine manner. Routine immunizations against common childhood infections and annual influenza immunization can also help prevent any secondary infections from occurring.

Regular neuropsychological, audiologic, and ophthalmologic examinations are also recommended.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.

Unlike Borjeson-Forssman-Lehmann syndrome, a disorder that was determined to be very similar to WTS, the individuals with Wilson–Turner syndrome do not develop cataracts or hypermetropia later in life. By far, the most debilitating part of this disorder is intellectual disability. Many of the other symptoms are more easily managed through hormone treatment, proper diet and exercise, and speech therapy.