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Type 2 Diabetes Mellitus

Disease Details

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Description: Type 2 diabetes mellitus is a chronic condition characterized by insulin resistance and impaired insulin secretion, leading to elevated blood glucose levels.
Type: Type 2 diabetes mellitus is primarily a metabolic disorder. Its genetic transmission is complex and multifactorial, involving multiple genes and environmental factors. There is no single pattern of inheritance, but a family history of the condition significantly increases the risk.
Signs And Symptoms: The classic symptoms of diabetes are frequent urination (polyuria), increased thirst (polydipsia), increased hunger (polyphagia), and weight loss. Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, recurrent vaginal infections, and fatigue. Other symptoms may include loss of taste. Many people, however, have no symptoms during the first few years and are diagnosed on routine testing. A small number of people with type 2 diabetes can develop a hyperosmolar hyperglycemic state (a condition of very high blood sugar associated with a decreased level of consciousness and low blood pressure).
Prognosis: For type 2 diabetes mellitus, the prognosis varies depending on several factors, including how well blood sugar levels are managed, the presence of other health conditions, and the patient's adherence to treatment plans. Proper management, including medication, lifestyle changes, and regular medical check-ups, can significantly improve outcomes and reduce the risk of complications such as cardiovascular disease, neuropathy, nephropathy, and retinopathy. Uncontrolled diabetes can lead to severe health complications and a reduced life expectancy. Early detection and consistent management are key to a better prognosis.
Onset: Type 2 diabetes mellitus typically has a gradual onset, often developing over several years. It is most commonly diagnosed in adults over the age of 45, although it is increasingly seen in younger individuals due to rising obesity rates and sedentary lifestyles.
Prevalence: Type 2 diabetes mellitus is a chronic condition characterized by insulin resistance and relative insulin deficiency. It is one of the most common diseases worldwide, affecting hundreds of millions of people. The prevalence of type 2 diabetes has been increasing over the years, largely due to rising rates of obesity and lifestyle changes.

### Key Points:
- **Global prevalence**: As of current estimates, more than 400 million adults have type 2 diabetes globally.
- **Percentage**: Approximately 8-12% of the global adult population is affected.
- **Rising trend**: The prevalence is projected to increase significantly, reaching around 700 million by 2045.

Efforts to manage and prevent type 2 diabetes focus on lifestyle interventions, such as diet and exercise, as well as medication and regular monitoring of blood glucose levels.
Epidemiology: The International Diabetes Federation estimates nearly 537 million people lived with diabetes worldwide in 2021, 90–95% of whom have type 2 diabetes. Diabetes is common both in the developed and the developing world.Some ethnic groups such as South Asians, Pacific Islanders, Latinos, and Native Americans are at particularly high risk of developing type 2 diabetes. Type 2 diabetes in normal weight individuals represents 60 to 80 percent of all cases in some Asian countries. The mechanism causing diabetes in non-obese individuals is poorly understood.Rates of diabetes in 1985 were estimated at 30 million, increasing to 135 million in 1995 and 217 million in 2005. This increase is believed to be primarily due to the global population aging, a decrease in exercise, and increasing rates of obesity. Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel with rising obesity rates. The five countries with the greatest number of people with diabetes as of 2000 are India having 31.7 million, China 20.8 million, the United States 17.7 million, Indonesia 8.4 million, and Japan 6.8 million. It is recognized as a global epidemic by the World Health Organization.
Intractability: Type 2 diabetes mellitus is generally considered a chronic condition, meaning it can be managed but not cured. Effective management strategies include lifestyle changes such as diet, exercise, and weight loss, as well as medications to control blood glucose levels. While it is not "intractable" in the sense that it can be managed successfully in many people, it requires ongoing treatment and monitoring. In some cases, complications may arise that can make management more challenging.
Disease Severity: Type 2 diabetes mellitus is a chronic condition where the body either resists the effects of insulin or doesn't produce enough insulin to maintain normal glucose levels. Disease severity can range from mild to severe, and it can lead to various complications if poorly managed, such as cardiovascular disease, nerve damage, kidney damage, eye damage, and more. Regular monitoring and management are crucial to prevent complications.
Healthcare Professionals: Disease Ontology ID - DOID:9352
Pathophysiology: Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance. Insulin resistance, which is the inability of cells to respond adequately to normal levels of insulin, occurs primarily within the muscles, liver, and fat tissue. In the liver, insulin normally suppresses glucose release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood. The proportion of insulin resistance versus beta cell dysfunction differs among individuals, with some having primarily insulin resistance and only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.Other potentially important mechanisms associated with type 2 diabetes and insulin resistance include: increased breakdown of lipids within fat cells, resistance to and lack of incretin, high glucagon levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the central nervous system. However, not all people with insulin resistance develop diabetes since an impairment of insulin secretion by pancreatic beta cells is also required.In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for the insulin insensitivity. But when type 2 diabetes has become manifest, a type 2 diabetic will have lost about half of their beta cells.Fatty acids in the beta cells activate FOXO1, resulting in apoptosis of the beta cells.The causes of the aging-related insulin resistance seen in obesity and in type 2 diabetes are uncertain. Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance. New evidence also points to a role of a brain region called the hypothalamus in the development of insulin resistance. A gene called Dusp8 is linked with an increased risk for diabetes. This gene codes for a protein that regulates neuronal signaling in the hypothalamus. Also, infusions into the hypothalamus of a hormone called leptin normalize blood glucose and diminish insulin resistance in diabetic animals. Activation of hypothalamic cells by leptin has an important role in maintaining normal levels of blood glucose. Thus, both the endocrine cells of the pancreas AND cells in the hypothalamus may have a role in the etiology of type 2 diabetes.
Hypothalamic cells regulate blood glucose via projections to the autonomic nervous system. Autonomic innervation of liver and muscle cells stimulates an increased uptake of glucose. In diabetic humans, the control of blood glucose by the autonomic nervous system is abnormal. Leptin-sensitive, glucose regulating neurons become resistant to leptin during aging or during exposure to a high-fat diet. These leptin-resistant neurons fail to restrain food intake, obesity, and blood glucose. The reasons for this lowered responsiveness to leptin are uncertain and are part of the puzzle of the causes of type 2 diabetes.Blood glucose levels can also be normalized in diabetic rodents by a single intrahypothalamic infusion of Fibroblast Growth Factor 1 (FGF1), an effect that persists for months even in severely diabetic animals. This remarkable cure of diabetes is accomplished by a stimulation of accessory brain cells called astrocytes. Hypothalamic astrocytes that produce Fatty Acid Binding Protein 7 (FABP7) are targets of FGF1; these cells are also in close contact with leptin-sensitive neurons, influence their function, and regulate leptin sensitivity. An abnormal function of FABP7+ astrocytes thus may contribute to the resistance to leptin and insulin that appear during aging and during exposure to high-fat diets.
During aging, FABP7+ astrocytes develop cytoplasmic granules derived from degenerating mitochondria. This mitochondrial degeneration is partly due to the oxidative stress of the heightened amounts of fatty acids that are taken up by these cells and oxidized within mitochondria. A pathological degeneration of mitochondria in these cells may compromise their normal functions and contribute to abnormalities in the control of blood glucose by the hypothalamus.
Carrier Status: Type 2 diabetes mellitus is not a condition with a carrier status like some genetic disorders. It is a complex, multifactorial disease influenced by genetic, environmental, and lifestyle factors. Certain genetic predispositions can increase the risk, but it is mostly managed through lifestyle modifications and medical interventions.
Mechanism: Type 2 diabetes mellitus primarily involves insulin resistance and pancreatic β-cell dysfunction.

**Mechanism**:
1. **Insulin Resistance**: Target cells in muscles, liver, and fat tissue show decreased sensitivity to insulin. As a result, glucose uptake is impaired, and blood glucose levels remain high.
2. **β-cell Dysfunction**: Pancreatic β-cells are unable to adequately compensate for insulin resistance by increasing insulin secretion, leading to insufficient insulin levels.

**Molecular Mechanisms**:
1. **Insulin Signaling Pathway Impairment**: The insulin receptor and downstream signaling elements (e.g., IRS proteins, PI3K, and Akt) are dysfunctional, reducing glucose uptake and glycogen synthesis.
2. **Free Fatty Acids (FFAs)**: Elevated circulating FFAs contribute to insulin resistance and β-cell apoptosis through mechanisms like increased oxidative stress and lipid accumulation in non-adipose tissues.
3. **Inflammatory Cytokines**: Chronic inflammation, often associated with obesity, leads to increased levels of TNF-α, IL-6, which interfere with insulin signaling.
4. **ER Stress**: Unfolded protein response activation in β-cells leads to apoptosis and reduced insulin secretion.
5. **Adipokines**: Imbalanced adipokines (e.g., decreased adiponectin and increased resistin) alter insulin sensitivity.
6. **Genetic Factors**: Polymorphisms in genes related to β-cell function and insulin signaling contribute to disease susceptibility.

Understanding these mechanisms highlights the complexity and multifactorial nature of type 2 diabetes mellitus.
Treatment: For type 2 diabetes mellitus, treatment approaches typically include:

1. **Lifestyle Modifications**
- **Diet:** Emphasis on balanced meals rich in vegetables, whole grains, lean proteins, and healthy fats; reduction in refined sugars and processed foods.
- **Exercise:** Regular physical activity, such as 150 minutes of moderate aerobic exercise per week.
- **Weight Management:** Achieving and maintaining a healthy weight.

2. **Medications**
- **Oral Hypoglycemics:** Metformin is commonly the first-line medication.
- **Other Medications:** Sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors, and thiazolidinediones.
- **Insulin Therapy:** May be necessary for some individuals, particularly if blood glucose levels are not managed with oral medications and lifestyle changes.

3. **Blood Sugar Monitoring**
- Regular monitoring of blood glucose levels to track and manage glucose control.

4. **Education and Support**
- Diabetes education programs to help with understanding disease management.
- Support from healthcare providers, nutritionists, and peer groups.
Compassionate Use Treatment: Compassionate use treatment refers to the access of investigational drugs outside of clinical trials for patients with serious or immediately life-threatening conditions who have no other treatment options. For type 2 diabetes mellitus, compassionate use is less commonly invoked compared to terminal illnesses, but some innovative treatments might be accessed this way in rare cases.

Off-label treatments for type 2 diabetes mellitus involve using medications approved for other conditions or indications. Some examples include:
- **SGLT2 inhibitors**: Originally approved as glucose-lowering agents, some are being investigated for off-label use to address heart failure and chronic kidney disease in diabetic patients.
- **GLP-1 receptor agonists**: Also used for weight management in individuals without diabetes but with obesity, which can benefit those with type 2 diabetes.
- **Metformin**: While widely used for diabetes, it’s also used off-label in conditions like polycystic ovary syndrome (PCOS).

Experimental treatments can include a wide variety of innovative approaches under investigation:
- **Stem cell therapy**: Research is ongoing to determine the potential for stem cells to regenerate insulin-producing cells.
- **Gene therapy**: Experimental approaches aim to modify or correct genetic predispositions to improve regulation of blood sugar levels.
- **Artificial pancreas systems**: Combining continuous glucose monitors with insulin pumps to automate insulin delivery.

These treatments are generally in various phases of clinical trials and must undergo rigorous testing before becoming widely available.
Lifestyle Recommendations: For type 2 diabetes mellitus, lifestyle recommendations are essential for management and include:

1. **Healthy Eating:** Emphasize a balanced diet rich in vegetables, whole grains, lean proteins, and healthy fats. Limit sugar and refined carbohydrates.

2. **Regular Physical Activity:** Aim for at least 150 minutes of moderate-intensity aerobic exercise per week, such as brisk walking or swimming, along with strength training twice a week.

3. **Weight Management:** Achieve and maintain a healthy weight through diet and exercise, as weight loss can improve insulin sensitivity and blood glucose control.

4. **Monitoring Blood Sugar:** Regularly check blood glucose levels as advised by your healthcare provider to manage and detect any changes early.

5. **Quit Smoking:** Smoking cessation is critical as smoking exacerbates the risk of complications from diabetes.

6. **Limit Alcohol:** Consume alcohol in moderation, and be aware of its effects on blood glucose levels.

7. **Stress Management:** Practice stress-reducing activities like mindfulness, yoga, or relaxation techniques to help maintain stable blood glucose levels.

Adhering to these lifestyle recommendations can significantly aid in managing type 2 diabetes mellitus and reducing the risk of complications.
Medication: For type 2 diabetes mellitus, medications may include:

1. **Metformin:** Often the first-line treatment, it reduces glucose production in the liver and improves insulin sensitivity.
2. **Sulfonylureas:** Such as glipizide and glyburide, these increase insulin production by the pancreas.
3. **Thiazolidinediones:** Like pioglitazone, they enhance insulin sensitivity in fat and muscle tissues.
4. **DPP-4 Inhibitors:** Such as sitagliptin, they increase insulin release and decrease glucagon levels.
5. **SGLT2 Inhibitors:** Such as canagliflozin, they prevent glucose reabsorption in the kidneys, leading to glucose excretion in urine.
6. **GLP-1 Receptor Agonists:** Like liraglutide, they slow gastric emptying, increase insulin secretion, and decrease glucagon secretion.
7. **Insulin:** May be required for some patients to control blood glucose levels.

Management often involves lifestyle changes, such as improved diet and increased physical activity, along with these medications.
Repurposable Drugs: Currently, several repurposable drugs are being investigated for managing type 2 diabetes mellitus beyond their original indications. Some of these include:

1. **Metformin**: Originally an anti-diabetic drug, it's also explored for its anti-aging and anti-cancer properties.
2. **SGLT2 Inhibitors**: These drugs, initially designed for diabetes, are being repurposed for heart failure and chronic kidney disease.
3. **GLP-1 Receptor Agonists**: While primarily for diabetes, they are also studied for obesity and neurodegenerative disorders like Alzheimer's disease.
4. **Statins**: Primarily used for lowering cholesterol, statins are also being researched for potential benefits in improving insulin sensitivity and cardiovascular outcomes in diabetics.
5. **ACE Inhibitors**: Typically used for hypertension, they may also provide renal protective effects in diabetic patients.
6. **DPP-4 Inhibitors**: Apart from diabetes, these are being evaluated for their potential anti-inflammatory effects.

These examples highlight the potential for existing medications to offer additional therapeutic benefits in managing type 2 diabetes mellitus and its complications.
Metabolites: For type 2 diabetes mellitus, common altered metabolites include glucose, insulin, free fatty acids, amino acids (such as branched-chain amino acids), and acylcarnitines. These changes reflect the metabolic dysregulation and insulin resistance characteristic of the disease.
Nutraceuticals: For type 2 diabetes mellitus, nutraceuticals refer to bioactive compounds derived from foods that offer medical or health benefits. Examples include omega-3 fatty acids, soluble fiber, vitamins (like vitamin D), and antioxidants (such as polyphenols found in green tea). These substances can help improve insulin sensitivity, control blood glucose levels, and reduce inflammation. However, their efficacy can vary, and they should complement, not replace, standard medical treatments.

"NAN" in this context might refer to Nutritional Assessment and Nutraceuticals, though it is not a standard abbreviation in medical terminology. If it pertains to a specific brand, product, or concept, please provide additional details for more accurate information.
Peptides: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and relative insulin deficiency. Peptides in the context of T2DM commonly refer to several types:

1. **Insulin** - A peptide hormone used in advanced stages of T2DM to control blood glucose levels.
2. **C-peptide** - A byproduct of insulin production, used to evaluate endogenous insulin production.
3. **Amylin** - A peptide hormone co-secreted with insulin, influencing glucose regulation.
4. **GLP-1 (Glucagon-like peptide-1)** - An incretin hormone that stimulates insulin secretion, inhibits glucagon release, and slows gastric emptying.

Nanotechnology (nan) in T2DM focuses on enhancing drug delivery, developing nanoscale sensors for glucose monitoring, and creating advanced biomaterials for insulin delivery systems to improve glycemic control and patient compliance.