Sedentary lifestyle increases the likelihood of development of insulin resistance. It has been estimated that each 500 kcal/week increment in physical activity related energy expenditure, reduces the lifetime risk of type 2 diabetes by 9%. A different study found that vigorous exercise at least once a week reduced the risk of type 2 diabetes in women by 33%.

Several associated risk factors include the following:

- Genetic factors (inherited component):

- Family history of type 2 diabetes

- Insulin receptor mutations (Donohue syndrome)

- LMNA mutations (familial partial lipodystrophy)

- Cultural variables, such as diet varying with race and class; factors related to stress, socio-economic status and history have been shown to activate the stress response, which increases the production of glucose and insulin resistance, as well as inhibiting pancreatic function and thus might be of importance, although it is not fully corroborated by the scientific evidence.

- Particular physiological conditions and environmental factors:

- Age 40–45 years or older

- Obesity

- The tendency to store fat preferentially in the abdomen (also known as "abdominal obesity)", as opposed to storing it in hips and thighs

- Sedentary lifestyle, lack of physical exercise

- Hypertension

- High triglyceride level (hypertriglyceridemia)

- Low level of high-density lipoprotein (also known as HDL cholesterol or "good cholesterol")

- Prediabetes, blood glucose levels have been too high in the past, i.e. the patient's body has previously shown slight problems with its production and usage of insulin ("previous evidence of impaired glucose homeostasis")

- Having developed gestational diabetes during past pregnancies

- Giving birth to a baby weighing more than 9 pounds (a bit over 4 kilograms)

- Pathology:

- Obesity and overweight (BMI > 25)

- Metabolic syndrome (hyperlipidemia + HDL cholesterol level 2.82 mmol/L), hypertension (> 140/90 mmHg), or arteriosclerosis

- Liver pathologies

- Infection (Hepatitis C)

- Hemochromatosis

- Gastroparesis

- Polycystic ovary syndrome (PCOS)

- Hypercortisolism (e.g., Cushing's syndrome, glucocorticoid therapy)

- Medications (e.g., glucosamine, rifampicin, isoniazid, olanzapine, risperidone, progestogens, glucocorticoids, methadone, many antiretrovirals)

In 2016 the United States Preventive Services Task Force concluded that testing the general population under the age of 40 without symptoms is of unclear benefit.

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.

These unclassified forms are extremely rare:

- Hyperalphalipoproteinemia

- Polygenic hypercholesterolemia

Diet has an effect on blood cholesterol, but the size of this effect varies between individuals. Moreover, when dietary cholesterol intake goes down, production (principally by the liver) typically increases, so that blood cholesterol changes can be modest or even elevated. This compensatory response may explain hypercholesterolemia in anorexia. A 2016 review found tentative evidence that dietary cholesterol is associated with higher blood cholesterol. Trans fats have been shown to reduce levels of HDL while increasing levels of LDL. LDL and total cholesterol also increases by very high fructose intake.

Among people whose life expectancy is relatively short, hypercholesterolemia is not a risk factor for death by any cause including coronary heart disease. Among people older than 70, hypercholesterolemia is not a risk factor for being hospitalized with myocardial infarction or angina. There are also increased risks in people older than 85 in the use of statin drugs. Because of this, medications which lower lipid levels should not be routinely used among people with limited life expectancy.

The American College of Physicians recommends for hypercholesterolemia in people with diabetes:

1. Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all adults with known coronary artery disease and type 2 diabetes.

2. Statins should be used for primary prevention against macrovascular complications in adults with type 2 diabetes and other cardiovascular risk factors.

3. Once lipid-lowering therapy is initiated, people with type 2 diabetes mellitus should be taking at least moderate doses of a statin.

4. For those people with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.

Developmental delay is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Normal neuronal and muscle cells do not express glucose-6-phosphatase, so GSD I causes no other neuromuscular effects.

Hypertriglyceridemia denotes high ("hyper-") blood levels ("-emia") of triglycerides, the most abundant fatty molecule in most organisms. Elevated levels of triglycerides are associated with atherosclerosis, even in the absence of hypercholesterolemia (high cholesterol levels), and predispose to cardiovascular disease. Very high triglyceride levels also increase the risk of acute pancreatitis. Hypertriglyceridemia itself is usually symptomless, although high levels may be associated with skin lesions known as "xanthomas".

The diagnosis is made on blood tests, often performed as part of screening. Once diagnosed, other blood tests are usually required to determine whether the raised triglyceride level is caused by other underlying disorders ("secondary hypertriglyceridemia") or whether no such underlying cause exists ("primary hypertriglyceridaemia"). There is a hereditary predisposition to both primary and secondary hypertriglyceridemia.

Weight loss and dietary modification may improve hypertriglyceridemia. The decision to treat hypertriglyceridemia with medication depends on the levels and on the presence of other risk factors for cardiovascular disease. Very high levels that would increase the risk of pancreatitis is treated with a drug from the fibrate class. Niacin and omega-3 fatty acids as well as drugs from the statin class may be used in conjunction, with statins being the main drug treatment for moderate hypertriglyceridemia where reduction of cardiovascular risk is required.

A further effect of chronic lactic acidosis in GSD I is hyperuricemia, as lactic acid and uric acid compete for the same renal tubular transport mechanism. Increased purine catabolism is an additional contributing factor. Uric acid levels of 6–12 mg/dl are typical of GSD I. Allopurinol may be needed to prevent uric acid nephropathy and gout.

In February 2013 scientists successfully cured type 1 diabetes in dogs using a pioneering gene therapy.

At present, there is no international standard classification of diabetes in dogs. Commonly used terms are:

- Insulin deficiency diabetes or primary diabetes, which refers to the destruction of the beta cells of the pancreas and their inability to produce insulin.

- Insulin resistance diabetes or secondary diabetes, which describes the resistance to insulin caused by other medical conditions or by hormonal drugs.

While the occurrence of beta cell destruction is known, all of the processes behind it are not. Canine primary diabetes mirrors Type 1 human diabetes in the inability to produce insulin and the need for exogenous replacement of it, but the target of canine diabetes autoantibodies has yet to be identified. Breed and treatment studies have been able to provide some evidence of a genetic connection. Studies have furnished evidence that canine diabetes has a seasonal connection not unlike its human Type 1 diabetes counterpart, and a "lifestyle" factor, with pancreatitis being a clear cause. This evidence suggests that the disease in dogs has some environmental and dietary factors involved.

Secondary diabetes may be caused by use of steroid medications, the hormones of estrus, acromegaly, (spaying can resolve the diabetes), pregnancy, or other medical conditions such as Cushing's disease. In such cases, it may be possible to treat the primary medical problem and revert the animal to non-diabetic status. Returning to non-diabetic status depends on the amount of damage the pancreatic insulin-producing beta cells have sustained.

It happens rarely, but it is possible for a pancreatitis attack to activate the endocrine portion of the organ back into being capable of producing insulin once again in dogs. It is possible for acute pancreatitis to cause a temporary, or transient diabetes, most likely due to damage to the endocrine portion's beta cells. Insulin resistance that can follow a pancreatitis attack may last for some time thereafter. Pancreatitis can damage the endocrine pancreas to the point where the diabetes is permanent.

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.

Researchers from the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducted a study and found that early-onset paternal obesity is connected with an increased risk of liver disease in their kin. Researchers found that obese fathers had an elevated level of serum alanine aminotransferase (ALT), a liver enzyme, compared to fathers who were not obese. They did a secondary analysis that excluded obese offspring. Children who were a normal weight but had obese fathers still had elevated ALT levels, which indicated that a child's ALT levels are not dependent upon the child's own BMI.

Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin), can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.

Obese women have an increased risk of pregnancy-related complications, including hypertension, gestational diabetes, and blood clots. Also, the mother is at risk of going into preterm labor. Maternal obesity is also known to be associated with increased rates of complications in late pregnancy such as cesarean delivery, and shoulder dystocia. A meta-analysis estimated that Cesarean delivery rates increased with odds ratios of 1.5 among overweight, 2 among obese, and 3 among severely obese women, compared with normal weight pregnant women. In addition, morbidly obese women who have not had children before are at increased risk of all–cause preterm deliveries. It is well recognized that obese women are at increased risk of preeclampsia and that women who have never been pregnant are at higher risk of preeclampsia than women who have had children in the past.

In some forms of MODY, standard treatment is appropriate, though exceptions occur:

- In MODY2, oral agents are relatively ineffective and insulin is unnecessary.

- In MODY1 and MODY3, insulin may be more effective than drugs to increase insulin sensitivity.

- Sulfonylureas are effective in the K channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested that the reduced clearance of sulfonylureas stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently to the mouse model and that there was no consistent decrease in the clearance of sulfonylureas in randomly selected HNF1A-MODY and HNF4A-MODY patients.

The two forms of this lipid disorder are:

- Familial combined hyperlipidemia (FCH) is the familial occurrence of this disorder, probably caused by decreased LDL receptor and increased ApoB.

- Acquired combined hyperlipidemia is extremely common in patients who suffer from other diseases from the metabolic syndrome ("syndrome X", incorporating diabetes mellitus type II, hypertension, central obesity and CH). Excessive free fatty acid production by various tissues leads to increased VLDL synthesis by the liver. Initially, most VLDL is converted into LDL until this mechanism is saturated, after which VLDL levels elevate.

Some sources make a distinction between two forms of monogenetic diabetes: MODY and neonatal diabetes. However, they have much in common and are often studied together.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, "bad cholesterol"), in the blood and early cardiovascular disease. Since individuals with FH underlying body biochemistry is slightly different, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH (such as dietary modification and statin tablets). Nevertheless, treatment (including higher statin doses) is usually effective.

FH is classified as a type 2 familial dyslipidemia. There are five types of familial dyslipidemia (not including subtypes), and each are classified from both the altered lipid profile and by the genetic abnormality. For example, high LDL (often due to LDL receptor defect) is type 2. Others include defects in chylomicron metabolism, triglyceride metabolism, and metabolism of other cholesterol-containing particles, such as VLDL and IDL.

About 1 in 300 to 500 people have mutations in the "LDLR" gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare. People who have one abnormal copy (are heterozygous) of the "LDLR" gene may develop cardiovascular disease prematurely at the age of 30 to 40. Having two abnormal copies (being "homozygous") may cause severe cardiovascular disease in childhood. Heterozygous FH is a common genetic disorder, inherited in an autosomal dominant pattern, occurring in 1:500 people in most countries; homozygous FH is much rarer, occurring in 1 in a million births.

Heterozygous FH is normally treated with statins, bile acid sequestrants, or other lipid lowering agents that lower cholesterol levels. New cases are generally offered genetic counseling. Homozygous FH often does not respond to medical therapy and may require other treatments, including LDL apheresis (removal of LDL in a method similar to dialysis) and occasionally liver transplantation.

Obesity is one of the leading preventable causes of death worldwide. A number of reviews have found that mortality risk is lowest at a BMI of 20–25 kg/m in non-smokers and at 24–27 kg/m in current smokers, with risk increasing along with changes in either direction. This appears to apply in at least four continents. In contrast, a 2013 review found that grade 1 obesity (BMI 30-35) was not associated with higher mortality than normal weight, and that overweight (BMI 25-30) was associated with "lower" mortality than was normal weight (BMI 18.5-25). Other evidence suggests that the association of BMI and waist circumference with mortality is U- or J-shaped, while the association between waist-to-hip ratio and waist-to-height ratio with mortality is more positive. In Asians the risk of negative health effects begins to increase between 22–25 kg/m. A BMI above 32 kg/m has been associated with a doubled mortality rate among women over a 16-year period. In the United States, obesity is estimated to cause 111,909 to 365,000 deaths per year, while 1 million (7.7%) of deaths in Europe are attributed to excess weight. On average, obesity reduces life expectancy by six to seven years, a BMI of 30–35 kg/m reduces life expectancy by two to four years, while severe obesity (BMI > 40 kg/m) reduces life expectancy by ten years.

Obesity increases the risk of many physical and mental conditions. These comorbidities are most commonly shown in metabolic syndrome, a combination of medical disorders which includes: diabetes mellitus type 2, high blood pressure, high blood cholesterol, and high triglyceride levels.

Complications are either directly caused by obesity or indirectly related through mechanisms sharing a common cause such as a poor diet or a sedentary lifestyle. The strength of the link between obesity and specific conditions varies. One of the strongest is the link with type 2 diabetes. Excess body fat underlies 64% of cases of diabetes in men and 77% of cases in women.

Health consequences fall into two broad categories: those attributable to the effects of increased fat mass (such as osteoarthritis, obstructive sleep apnea, social stigmatization) and those due to the increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease). Increases in body fat alter the body's response to insulin, potentially leading to insulin resistance. Increased fat also creates a proinflammatory state, and a prothrombotic state.

No sexual predilection is observed because the deficiency of glycogen synthetase activity is inherited as an autosomal recessive trait.

The overall frequency of glycogen-storage disease is approximately 1 case per 20,000–25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. The identification of asymptomatic and oligosymptomatic siblings in several glycogen-storage disease type 0 families has suggested that glycogen-storage disease type 0 is underdiagnosed.

Around 80 cases have been reported in the literature worldwide, hence this condition appears to be relatively rare. More than likely, sitosterolemia is significantly underdiagnosed and many patients are probably misdiagnosed with hyperlipidemia.