Chronic hyperglycemia caused by abnormalities in insulin secretion, insulin action, or both characterises the group of metabolic illnesses known as diabetes mellitus.
Chronic hyperglycemia caused by abnormalities in insulin secretion, insulin action, or both characterises the group of metabolic illnesses known as diabetes mellitus. Because insulin is important as an anabolic hormone, there are metabolic irregularities in carbs, lipids, and proteins.
These metabolic abnormalities are brought on by insufficient insulin levels to produce an adequate response and/or insulin resistance of the target tissues, primarily the skeletal muscles, adipose tissue, and to a lesser extent, the liver, at the level of insulin receptors, signal transduction system, and/or effector enzymes or genes. The kind and length of diabetes determine how severe the symptoms are.
If untreated, uncontrolled diabetes can cause coma, stupor, and, in rare cases, death from nonketotic hyperosmolar syndrome or ketoacidosis.
Classification of diabetes mellitus
Although categorising diabetes is crucial and affects treatment methods, it is not always simple to do so, especially for younger persons. Additionally, 10% of those first categorised may need to be reclassified.
The basic classification of diabetes—type 1, type 2, other forms, and gestational diabetes mellitus (GDM)—proposed by the American Diabetes Association (ADA) in 1997 is still the most widely used and was adopted by ADA."Type 1 and type 2 diabetes are the same disorder of insulin resistance set against different genetic backgrounds," asserts Wilkin, who proposed the accelerator theory.
Increased height growth rate and decreased cell sensitivity to glucose are two additional indicators of type 1 diabetes.Despite the inconsistent results of clinical trials using antioxidants in the management of diabetes, the implications of elevated free radicals, oxidative stress, and numerous metabolic stressors in the pathogenesis, development, and complications of diabetes mellitus are very strong and well documented.
Since it has been established that induced oxidative stress results in the loss of beta cells in ER-knockout mice, the female hormone 17-estradiol, which acts through the oestrogen receptor (ER), is crucial for the growth and maintenance of pancreatic cell function. By defending pancreatic islets against glucolipotoxicity, the ER-receptor activation avoids -cell malfunction.
Type 1 diabetes mellitus
Autoimmune type 1 diabetes
The primary cause of type 1 diabetes is an autoimmune attack on pancreatic cells that involves both a humoral (B cell) and T-cell driven inflammatory response (insulitis). Although it is unclear how these antibodies contribute to the aetiology of the disease, the existence of autoantibodies against the pancreatic islet cells is a defining feature of type 1 diabetes.
These autoantibodies include islet cell autoantibodies, autoantibodies to insulin (IAA), protein tyrosine phosphatase (IA2 and IA2), glutamic acid decarboxylase (GAD, GAD65), and zinc transporter protein (ZnT8A).These pancreatic autoantibodies, which are signs of type 1 diabetes, might be found in the serum of these patients months or years before the disease manifested itself.
Idiopathic type 1 diabetes
It has been claimed that there is a rare variant of type 1 diabetes called idiopathic, which is not caused by autoimmunity and is less severe than autoimmune type 1 diabetes. The majority of individuals with this kind are of African or Asian heritage and experience variable degrees of insulin insufficiency and episodic ketoacidosis.
Fulminant type 1 diabetes
With its non-immune mediated nature and different traits from idiopathic type 1 diabetes, this variant of type 1 diabetes was first identified in 2000.High glucose levels ( 288 mg/dL) and undetectable blood C-peptide levels, a marker of endogenous insulin production, are its defining features.
Ketoacidosis occurs shortly after the beginning of hyperglycemia. It has primarily been studied in East Asian nations and accounts for 5000–7000 instances, or 20% of acute-onset type 1 diabetes patients in Japan, with an incredibly quick and practically total beta-cell death and almost no residual insulin secretion.
Type 2 diabetes mellitus
According to a report released in 2013 by the IDF, the global prevalence of diabetes in adults (20-79 years old) was 8.3% (382 million people), with 14 million more men than women (198 million men vs 184 million women), the majority between the ages of 40 and 59 years, and the number is expected to increase beyond 592 million by 2035 with a 10.1% global prevalence.
Over half a billion people worldwide have diabetes, with 175 million cases still going undiagnosed. Pregnancy-related hyperglycemia affects an extra 21 million women.
Patients with type 2 diabetes who have insulin resistance need more insulin in the insulin-target tissues. In Urine Albumin addition to insulin resistance, the pancreatic cells' dysfunction prevented them from supplying the extra demand for insulin.
On the other hand, due to the slow cell death, insulin secretion diminishes over time as the need for insulin rises, which may cause some type 2 diabetes patients who were previously independent to become reliant on insulin.
The majority of type 2 diabetes patients continue to secrete insulin and rarely experience insulin depletion, indicating that they are not dependent on it. One of the main distinctions between type 2 diabetes and type 1 diabetes is the need on insulin.
Both type 1 and type 2 diabetes have a genetic propensity, however type 2 has a stronger genetic basis whereas type 1's genes are better understood (the TCF7L2 gene is closely linked to type 2 diabetes).Particularly HDL Cholesterol in nations where routine checkups without symptoms are not part of the culture, type 2 diabetes diagnosis is typically delayed for years because of its modest initial symptoms.
Metabolic illnesses, including diabetes, are thought to occur as a result of defects in the insulin-dependent substrate proteins IRS-1 and IRS-2 driven signalling pathway. The insulin receptor C Peptide substrate (IRS) proteins, which are involved in the metabolic response to insulin, contain a large number of Ser/Thr residues that are phosphorylated by a large number of insulin-stimulated protein kinases, such as the serine/threonine kinase AKT and protein kinase C (PKC).
The development of diabetes and its main symptoms, such as hyperinsulinemia, dyslipidemia, and insulin resistance, are all correlated with disruption in the AKT and PKC kinases.Genetically replacing the wild-type IRS-1 with a mutant version of the protein that has alanine instead of tyrosine in three places demonstrated the crucial part that IRS-1 phosphorylation plays in the emergence of insulin resistance.
HbA1c or FPG estimate of plasma glucose (or OGTT) are two methods used to identify diabetes mellitus. The estimated cutoff points for glucose and HbA1c are based on the correlation between FPG or HbA1c and retinopathy. Diagnosis of diabetes mellitus requires a blood fasting plasma glucose of less than 126 mg/dL (7.0 mmol/L), a 2-h OGTT plasma glucose of more than 200 mg/dL (11.1 mmol/L), a HbA1c of less than 6.5% (48 mmol/mol), or a random plasma glucose of more than 200 mg/dL (11.1 mmol/L) combined with symptoms of hyperglycemia.
The International Expert Committee in 2009 and the ADA both supported the use of HbA1c to diagnose diabetes in addition to monitoring treatment for the condition.
The pandemic of the century is diabetes mellitus, and the disease's prevalence will increase unless early-stage diagnostic procedures are used. This review concentrates on the different forms of diabetes and the efficient diagnostic techniques and standards to be applied for the diagnosis of diabetes and pre diabetes.
It is clear that a vast number of genes are involved in the development of diabetes, making it a complex disease. The accurate identification of the genetic causes of diabetes may be a crucial tool to enhance genetic counselling, patient-specific medication, and diagnosis.