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Diabetes Mellitus

Disease Details

Family Health Simplified

Description
Diabetes mellitus is a chronic condition characterized by high blood sugar levels due to the body's inability to produce or effectively use insulin.
Type
Diabetes mellitus includes several types, primarily Type 1 diabetes and Type 2 diabetes.

- Type 1 diabetes: This type has an autoimmune component and is influenced by multiple genes. It is typically inherited in a polygenic manner, meaning several genes may contribute to the risk.
- Type 2 diabetes: This type is more strongly associated with lifestyle factors but also has a genetic component. It is also inherited in a polygenic manner, with multiple genes contributing to the overall risk.

Gestational diabetes and other forms can also have genetic predispositions but are influenced by additional specific factors.
Signs And Symptoms
The classic symptoms of untreated diabetes are polyuria, thirst, and weight loss. Several other non-specific signs and symptoms may also occur, including fatigue, blurred vision, and genital itchiness due to Candida infection. About half of affected individuals may also be asymptomatic. Type 1 presents abruptly following a pre-clinical phase, while type 2 has a more insidious onset; patients may remain asymptomatic for many years.Diabetic ketoacidosis is a medical emergency that occurs most commonly in type 1, but may also occur in type 2 if it has been longstanding or if the individual has significant β-cell dysfunction. Excessive production of ketone bodies leads to signs and symptoms including nausea, vomiting, abdominal pain, the smell of acetone in the breath, deep breathing known as Kussmaul breathing, and in severe cases decreased level of consciousness. Hyperosmolar hyperglycemic state is another emergency characterised by dehydration secondary to severe hyperglycaemia, with resultant hypernatremia leading to an altered mental state and possibly coma.Hypoglycaemia is a recognised complication of insulin treatment used in diabetes. An acute presentation can include mild symptoms such as sweating, trembling, and palpitations, to more serious effects including impaired cognition, confusion, seizures, coma, and rarely death. Recurrent hypoglycaemic episodes may lower the glycaemic threshold at which symptoms occur, meaning mild symptoms may not appear before cognitive deterioration begins to occur.
Prognosis
The prognosis for diabetes mellitus varies depending on the type and how well it is managed. For type 1 diabetes, life expectancy can be near normal with rigorous blood sugar management, regular medical check-ups, and adjustments in lifestyle. For type 2 diabetes, the prognosis is generally better with early detection and proper management, including medication, diet, and exercise. However, poorly controlled diabetes of either type can lead to complications such as cardiovascular disease, kidney damage, neuropathy, and retinopathy, which can significantly impact quality of life and longevity. Regular monitoring and management are crucial for improving outcomes.
Onset
Diabetes mellitus can have different patterns of onset depending on its type:

1. **Type 1 Diabetes**: Onset is typically rapid in children and adolescents, often presenting with symptoms over a few weeks or months. This form is usually diagnosed in younger individuals but can occur at any age.

2. **Type 2 Diabetes**: Onset is generally gradual and often occurs in adults, particularly those over 45. However, the disease prevalence has been increasing among younger populations due to rising obesity rates. Symptoms may develop over several years and can be less noticeable.

3. **Gestational Diabetes**: This type occurs during pregnancy, typically identified through screening tests in the second trimester, between 24 and 28 weeks of gestation.

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Prevalence
Prevalence: Diabetes mellitus is a widespread condition, affecting approximately 463 million adults worldwide as of 2019, with the number expected to rise. Prevalence rates vary globally, with higher rates in some regions due to lifestyle factors and genetic predispositions.
Epidemiology
In 2017, 425 million people had diabetes worldwide, up from an estimated 382 million people in 2013 and from 108 million in 1980. Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.8% among adults, nearly double the rate of 4.7% in 1980. Type 2 makes up about 90% of the cases. Some data indicate rates are roughly equal in women and men, but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.The WHO estimates that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death. However another 2.2 million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes. For example, in 2017, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.0 million deaths worldwide, using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries, where more than 80% of diabetic deaths occur. The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030. The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet). The global number of diabetes cases might increase by 48% between 2017 and 2045.As of 2020, 38% of all US adults had prediabetes. Prediabetes is an early stage of diabetes.
Intractability
Diabetes mellitus is generally considered a manageable but chronic condition rather than intractable. With the right combination of lifestyle changes, medication, and ongoing medical care, many people with diabetes can control their blood glucose levels and prevent or delay complications. However, it cannot be completely cured, and management requires lifelong dedication.
Disease Severity
For diabetes mellitus, the disease severity can vary widely. It largely depends on factors such as how well blood glucose levels are controlled, the duration of the disease, and the presence of complications or co-morbidities. Poorly controlled diabetes can lead to severe complications, including cardiovascular disease, nerve damage, kidney failure, and vision problems, among others.

"Nan" usually refers to "nanometers," a scale for measuring very small objects, but it is not relevant in the context of diabetes mellitus, which is a condition involving blood glucose regulation.
Healthcare Professionals
Disease Ontology ID - DOID:9351
Pathophysiology
Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen (glycogenolysis), the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin.If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin resistance), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency.When there is too much glucose in the blood for a long time, the kidneys cannot absorb it all (reach a threshold of reabsorption) and the extra glucose gets passed out of the body through urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume is replaced osmotically from water in body cells and other body compartments, causing dehydration and increased thirst (polydipsia). In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).
Carrier Status
Diabetes mellitus is not a condition that involves carrier status, as it is not inherited in a simple Mendelian fashion like some genetic disorders. It is a complex metabolic disorder influenced by multiple genetic and environmental factors. The primary forms of diabetes mellitus are Type 1 diabetes, which is often considered an autoimmune condition, and Type 2 diabetes, which is largely influenced by lifestyle and genetic predisposition.
Mechanism
Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both.

### Mechanism:
1. **Type 1 Diabetes Mellitus (T1DM):**
- Caused by autoimmune destruction of pancreatic β-cells.
- Leads to an absolute deficiency of insulin.
- Onset typically occurs during childhood or adolescence.

2. **Type 2 Diabetes Mellitus (T2DM):**
- Results from a combination of insulin resistance and inadequate compensatory insulin secretion.
- The body’s cells become less responsive to insulin.
- Pancreatic β-cell dysfunction eventually occurs, leading to a relative insulin deficiency.
- Commonly associated with obesity and a sedentary lifestyle.

### Molecular Mechanisms:
1. **Type 1 Diabetes Mellitus:**
- Autoimmune response: Involves T-cells recognizing and attacking β-cell antigens (e.g., insulin, GAD65, IA-2).
- Genetic factors: HLA-DR3/DR4 alleles increase risk.
- Environmental triggers: Viral infections (e.g., Coxsackievirus) might initiate the autoimmune process.

2. **Type 2 Diabetes Mellitus:**
- Insulin resistance: Involves defects in insulin receptor signaling, particularly in muscle, liver, and adipose tissues.
- Key molecular players: Impaired phosphorylation of the insulin receptor and IRS proteins, reduced PI3K/Akt signaling.
- β-cell dysfunction: Increased demand on β-cells leads to apoptosis or functional impairment. Key genes involved include TCF7L2 and variants in KCNJ11.
- Inflammatory cytokines: TNF-α, IL-6, and others can exacerbate insulin resistance.
- Lipotoxicity and glucotoxicity: High levels of fatty acids and glucose can impair β-cell function and increase insulin resistance.

Understanding these mechanisms is crucial for developing targeted therapies and effective management strategies for diabetes mellitus.
Treatment
Diabetes mellitus treatment typically includes the following approaches:

1. **Lifestyle Changes**:
- **Diet**: Emphasis on a balanced diet low in sugars, refined carbohydrates, and saturated fats.
- **Exercise**: Regular physical activity to help control blood sugar levels and weight.
- **Weight Management**: Achieving and maintaining a healthy weight.

2. **Medications**:
- **Type 1 Diabetes**: Insulin therapy (injections or insulin pump).
- **Type 2 Diabetes**: Oral medications (e.g., metformin, sulfonylureas), and sometimes insulin or other injectable medications.

3. **Monitoring**:
- Regular blood sugar monitoring.
- Periodic HbA1c tests to measure long-term blood sugar control.

4. **Education**:
- Diabetes self-management education to help patients understand and manage their condition.

5. **Other Treatments**:
- Blood pressure and cholesterol control to reduce cardiovascular risk.
- Regular check-ups to monitor and manage complications.

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Compassionate Use Treatment
Compassionate use treatment for diabetes mellitus typically involves the use of investigational drugs or therapies that have not yet received regulatory approval but may benefit individuals with life-threatening or severely debilitating versions of the disease. This pathway allows patients to access new treatments when no satisfactory alternatives are available and when they cannot participate in clinical trials.

Off-label or experimental treatments for diabetes mellitus can include:

1. **SGLT2 Inhibitors:** While primarily approved for Type 2 diabetes, these drugs are occasionally used off-label for Type 1 diabetes under careful medical supervision.

2. **GLP-1 Receptor Agonists:** Similar to SGLT2 inhibitors, these are mainly for Type 2 diabetes but are sometimes considered for Type 1 or weight management.

3. **Metformin:** Though mainly for Type 2, metformin is occasionally used off-label in certain cases of Type 1 diabetes, particularly for insulin resistance and PCOS-associated diabetes.

4. **Artificial Pancreas Systems:** Experimental closed-loop insulin delivery systems that automatically adjust insulin levels in real-time are being explored.

5. **Islet Cell Transplantation:** This experimental procedure involves transplanting insulin-producing cells from a donor to the patient.

6. **Gene Therapy:** Currently in experimental stages, it aims to modify genes to either stimulate insulin production or correct underlying genetic defects.

7. **Stem Cell Therapy:** Research is ongoing to transform stem cells into insulin-producing beta cells.

While promising, these treatments often require further clinical trials to establish safety, efficacy, and regulatory approval. Usage should only occur under specialist supervision.
Lifestyle Recommendations
For diabetes mellitus, lifestyle recommendations include:

1. **Healthy Eating:** Focus on a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Limit intake of refined sugars and saturated fats.
2. **Regular Physical Activity:** Aim for at least 150 minutes of moderate-intensity exercise per week, such as brisk walking or cycling.
3. **Weight Management:** Maintain a healthy weight through diet and exercise to improve blood sugar control.
4. **Monitoring Blood Sugar:** Regularly check blood glucose levels as recommended by your healthcare provider.
5. **Medication Adherence:** Take medications as prescribed and consult with your doctor regarding any concerns.
6. **Avoid Smoking:** Smoking can exacerbate complications associated with diabetes.
7. **Limit Alcohol Intake:** Consume alcohol in moderation and be mindful of its impact on blood sugar levels.

These lifestyle changes can significantly help manage diabetes and reduce the risk of complications.
Medication
Medications commonly prescribed for diabetes mellitus include:

1. **Metformin** - Often the first-line treatment for type 2 diabetes, it helps reduce glucose production in the liver.
2. **Sulfonylureas** - Stimulate the pancreas to produce more insulin (e.g., glipizide, glyburide).
3. **Meglitinides** - Similar to sulfonylureas, they stimulate insulin production but have a shorter duration of action (e.g., repaglinide, nateglinide).
4. **Thiazolidinediones** - Improve insulin sensitivity (e.g., pioglitazone, rosiglitazone).
5. **DPP-4 Inhibitors** - Help to increase insulin release and decrease glucagon levels (e.g., sitagliptin, saxagliptin).
6. **SGLT2 Inhibitors** - Help the kidneys remove glucose from the bloodstream (e.g., canagliflozin, dapagliflozin).
7. **GLP-1 Receptor Agonists** - Increase insulin secretion, slow gastric emptying, and decrease appetite (e.g., liraglutide, exenatide).
8. **Insulin Therapy** - Necessary for type 1 diabetes and sometimes for type 2 diabetes, involving different types and regimens depending on the patient's needs (e.g., rapid-acting, long-acting insulin).

For more tailored and comprehensive treatment plans, consultation with a healthcare provider is essential.
Repurposable Drugs
For diabetes mellitus, some repurposable drugs include:

1. Metformin - originally developed for type 2 diabetes, it's being studied for cancer and aging.
2. GLP-1 receptor agonists (like liraglutide) - besides diabetes, they are being researched for obesity and cardiovascular benefits.
3. SGLT2 inhibitors (like empagliflozin) - while initially for diabetes, they show promise in heart failure and chronic kidney disease.

This highlights how medications can have versatile applications beyond their initial use.
Metabolites
In diabetes mellitus, key metabolites of interest include glucose, insulin, glycated hemoglobin (HbA1c), ketone bodies (such as acetoacetate and beta-hydroxybutyrate), and free fatty acids. Elevated blood glucose is a primary hallmark, while insulin levels may vary depending on the type of diabetes. Glycated hemoglobin is used to monitor long-term glucose control. Ketone bodies may be elevated in cases of diabetic ketoacidosis, a severe complication.
Nutraceuticals
Nutraceuticals are food-derived products that provide health benefits beyond basic nutrition, often used in the management of diabetes mellitus. Common nutraceuticals for diabetes include:

1. **Omega-3 Fatty Acids**: Found in fish oil, they may help improve lipid profiles and reduce inflammation.
2. **Alpha-Lipoic Acid**: An antioxidant that may help improve insulin sensitivity and reduce oxidative stress.
3. **Chromium**: This trace mineral may improve glucose metabolism and enhance the action of insulin.
4. **Cinnamon**: May lower blood glucose levels by improving insulin sensitivity.
5. **Fenugreek**: Contains soluble fiber which can help lower blood sugar levels.
6. **Bitter Melon**: May help lower blood glucose levels due to its insulin-like compounds.

While promising, the effectiveness and safety of these nutraceuticals can vary, and they should be used under the guidance of a healthcare provider to avoid potential interactions and side effects.
Peptides
Diabetes mellitus is characterized by impaired insulin production or action, leading to abnormal blood glucose levels. Peptides such as insulin and glucagon play crucial roles in managing this condition. Insulin helps reduce blood glucose levels by promoting its uptake into cells, while glucagon raises blood glucose levels by promoting glycogen breakdown. In some therapeutic approaches, insulin analogs (modified insulin peptides) are used to provide better control over blood glucose levels. Additionally, other peptides like GLP-1 (glucagon-like peptide-1) analogs are also used to enhance insulin secretion and glucose regulation.

Nanotechnology is emerging as a promising field in diabetes management. Nanomedicine developments include nanoparticle-based drug delivery systems that ensure more precise and sustained release of insulin and other antidiabetic drugs. Additionally, nanotechnology may lead to the creation of advanced glucose sensors and monitoring devices, improving diabetes management and patient compliance.