Scientists have developed a promising new drug that could prevent and even reverse the onset of type 1 diabetes. The experimental monoclonal antibody drug acts like a shield to protect insulin-producing cells from damage, even extending lifespan in some cases. Type 1 diabetes occurs when a patient’s immune system begins attacking the beta cells in their pancreas. These important cells produce insulin, and without them patients become unable to manage their blood glucose levels, resulting in a lifetime of managing injections and potential health complications….Continue reading…
By: Michael Irving
Source: NewAtlas
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Critics:
Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exception of insulin, most GLP receptor agonists (liraglutide, exenatide, and others), and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents.
There are different classes of anti-diabetic drugs, and their selection depends on the nature of diabetes, age, and situation of the person, as well as other factors. Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in type 1, which must be injected. Diabetes mellitus type 2 is a disease of insulin resistance by cells.
Type 2 diabetes mellitus is the most common type of diabetes. Treatments include agents that (1) increase the amount of insulin secreted by the pancreas, (2) increase the sensitivity of target organs to insulin, (3) decrease the rate at which glucose is absorbed from the gastrointestinal tract, and (4) increase the loss of glucose through urination.
Several groups of drugs, mostly given by mouth, are effective in type 2 diabetes, often in combination. The therapeutic combination in type 2 may include several insulin isoforms or oral antihyperglycemic agents. As of 2020, 23 unique antihyperglycemic drug combinations were approved by the FDA.
The first triple combination of oral anti-diabetics was approved in 2019, consisting of metformin, saxagliptin, and dapagliflozin. Another triple combination approval for metformin, linagliptin, and empagliflozin followed in 2020. Insulin is usually given subcutaneously, either by injections or by an insulin pump. In acute care settings, insulin may also be given intravenously.
Insulins are typically characterized by the rate at which they are metabolized by the body, yielding different peak times and durations of action. Faster-acting insulins peak quickly and are subsequently metabolized while longer-acting insulins tend to have extended peak times and remain active in the body for more significant periods.
Examples of rapid-acting insulins (peak at ~1 hour) are:
- Insulin lispro (Humalog)
- Insulin aspart (Novolog)
- Insulin glulisine (Apidra)
Examples of short-acting insulins (peak 2–4 hours) are:
- Regular insulin (Humulin R, Novolin R)
- Prompt insulin zinc (Semilente)
Examples of intermediate-acting insulins (peak 4–10 hours) are:
- Isophane insulin, neutral protamine Hagedorn (NPH) (Humulin N, Novolin N)
- Insulin zinc (Lente)
Examples of long-acting insulins (duration 24 hours, often without peak) are:
- Extended insulin zinc insulin (Ultralente)
- Insulin glargine (Lantus)
- Insulin detemir (Levemir)
- Insulin degludec (Tresiba)
Insulin degludec is sometimes classed separately as an “ultra-long” acting insulin due to its duration of action of about 42 hours, compared with 24 hours for most other long-acting insulin preparations.
As a systematic review of studies comparing insulin detemir, insulin glargine, insulin degludec and NPH insulin did not show any clear benefits or serious adverse effects for any particular form of insulin for nocturnal hypoglycemia, severe hypoglycemia, glycated hemoglobin A1c, non-fatal myocardial infarction/stroke, health-related quality of life or all-cause mortality.
The same review did not find any differences in effects of using these insulin analogues between adults and children. Most oral anti-diabetic agents are contraindicated in pregnancy, in which insulin is preferred. Insulin is not administered by other routes, although this has been studied. An inhaled form was briefly licensed but was subsequently withdrawn. Insulin sensitizers address the core problem in type 2 diabetes – insulin resistance.
Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Among common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain. Typical reduction in glycated hemoglobin (A1C) values for metformin is 1.5–2.0%
- Metformin (Glucophage) may be the best choice for patients who also have heart failure, but it should be temporarily discontinued before any radiographic procedure involving intravenous iodinatedcontrast, as patients are at an increased risk of lactic acidosis.
- Phenformin (DBI) was used from 1960s through 1980s, but was withdrawn due to lactic acidosis risk.
- Buformin also was withdrawn due to lactic acidosis risk.
Thiazolidinediones (TZDs), also known as “glitazones,” bind to PPARγ, peroxisome proliferator activated receptor γ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on peroxisome proliferator responsive elements (PPRE). The PPREs influence insulin-sensitive genes, which enhance production of mRNAs of insulin-dependent enzymes. Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production.
It is significantly less common than the three main types, constituting 1–2% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus, there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.
Some cases of diabetes are caused by the body’s tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis).
Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance (especially glucocorticoids which can provoke “steroid diabetes”). The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (ICD-10 code E12), was deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.
[72] Yet another form of diabetes that people may develop is double diabetes. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes.[73] It was first discovered in 1990 or 1991. There is no known preventive measure for type 1 diabetes. However, islet autoimmunity and multiple antibodies can be a strong predictor of the onset of type 1 diabetes.
Type 2 diabetes—which accounts for 85–90% of all cases worldwide—can often be prevented or delayed by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet.[2] Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish.
Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes. Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well. The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world.
There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.
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