The other specific types of diabetes are less common and can be broadly classed as genetic, exocrine pancreatic, endocrine, and drug-induced causes . A more comprehensive breakdown is provided in Table 1.2 and the more common types are discussed briefly later.
Classification of genetic disorders
With ongoing advances in the study of molecular genetics, there has been considerable progress in the identification of specific subtypes of diabetes of genetic origin. Through this work, it has been shown that the clinical subgroups are heterogeneous and there has been recognition of several novel, genetic-based syndromes associated with diabetes.The progress in our ability to examine genes to arrive at a diabetes diagnosis has improved treatment for these patients  and thus genetic diagnosis has become a key part of clinical management in many countries.
Genetic defects of beta-cell function
The diabetic state may be associated with monogenic defects in beta-cell function. These forms are characterized by onset of mild hyperglycemia during childhood or early adulthood, and include maturity-onset diabetes of the young (MODY), permanent neonatal diabetes (PNDM), transient neonatal diabetes (TNDM), and many other insulin-deficient syndromes with a myriad of other clinical features . The most well characterized of these is MODY. MODY is inherited in an autosomal dominant pattern and typically presents before the age of 25 years. While the condition results from beta-cell dysfunction, it is not always insulin dependent. Molecular genetic testing can define a diagnosis in 1–2% of all diabetic patients with monogenic diabetes. Advances in this field have led to the identification of the genes associated with many clinically identified subgroups of diabetes and explained clinical heterogeneity in conditions defined by age of diagnosis, for example neonatal diabetes and MODY. Molecular genetic tests are now available to help define the diagnosis, and importantly alter prognosis and optimize treatment of children, young adults and their families with diabetes.
Several mutations associated with MODY have been identified to date, of which the most common genetic subtypes are: GCK MODY, HNF1AMODY, HNF4AMODY, and IPF1MODY . These are listed in Table 1.2. Among these subtypes, the HNF1A MODY subtype is the most common and results in a progressive and marked hyperglycemia with a high risk of microvascular and macrovascular complications , but these patients respond well to sulfonylureas . Subtype HNF4A is similar to HNF1A but patients have marked macrosomia and transient neonatal hypoglycemia . The other subtype, GCKMODY, is a milder form of diabetes, characterized by a mild fasting hyperglycemia that is generally lifelong with little deterioration with age and does not requirement treatment [23,24].
In children less than 6 months of age, diabetes is more likely to be monogenic than autoimmune type 1 diabetes . However, in approximately 50% of these infants, the diabetes is transient (TNDM) . Further to the specific genetic types mentioned here, there are also many subtypes of neonatal diabetes which present as a result of multisystem clinical syndromes . For example, Wolfram syndrome, also referred to as DIDMOAD, is inherited by autosomal recessive trait, is a monogenic multisystem syndrome, and is characterized by marked beta-cell dysfunction .
Point mutations in mitochondrial DNA have been found to be associated with diabetes and sensori-neural deafness  and lead to a condition known as maternally inherited diabetes and deafness (MIDD). Genetic abnormalities that result in the inability to convert proinsulin to insulin have been identified in a few families. Usually such traits are inherited in an autosomal dominant pattern  and the resultant carbohydrate intolerance is mild.
Genetic defects in insulin action
Genetic defects in insulin action are rare, and the associated metabolic abnormalities may range from hyperinsulinemia and modest hyperglycemia to severe symptomatic diabetes resulting in death . Acanthosis nigricans may be present in some of these individuals. This syndrome was termed type A insulin resistance in the past. In such patients, diabetes only occurs when there is no beta-cell response to the insulin resistance.
Two pediatric syndromes that have mutations in the insulin receptor gene with subsequent alterations in insulin receptor function and extreme insulin resistance are called leprechaunism and the Rabson–Mendenhall syndrome . A heterogeneous group of disorders of lipid storage characterized by lipodystrophy, in which insulin resistance is a common feature, has also been described .
Diseases of the exocrine pancreas
Pancreatitis, trauma, infection, pancreatic carcinoma, and pancreatectomy are some of the acquired processes of the pancreas that can cause diabetes. Any process that diffusely injures the pancreas may cause diabetes . With the exception of cancer, damage to the pancreas must be extensive for diabetes to occur. However, adenocarcinomas that involve only a small portion of the pancreas have been associated with diabetes.This implies a mechanism other than a simple reduction in beta-cell mass . Hemochromatosis will also damage beta cells and impair insulin secretion . Fibrocalculous pancreatopathy may be accompanied by abdominal pain radiating to the back and pancreatic calcification on X-ray and ductal dilatation. Pancreatic fibrosis and calcified stones in the exocrine ducts are found at autopsy .
Insulin action can be antagonized by several hormones (e.g. growth hormone, cortisol, glucagon, epinephrine). Diseases associated with excess secretion of these hormones can cause diabetes (e.g. acromegaly, Cushing syndrome, glucagonoma and pheochromocytoma) . These forms of hyperglycemia resolve when the hormone excess is removed. Somatostatinoma and aldosteronoma-induced hypokalemia, can cause diabetes at least in part by inhibiting insulin secretion . Hyperglycemia generally resolves following successful removal of the tumor.
Drug-or chemical-induced diabetes
Insulin secretion may be impaired by many drugs. They may not, by themselves, cause diabetes but may precipitate diabetes in persons with insulin resistance . Pancreatic beta-cell destruction may occur with the use of certain toxins such as Vacor (a rat poison) , pentamidine , and some immunosuppressive drugs. Among these beta-cell toxic agents, the most commonly used are the immunosuppressive agents of which the calcineurin inhibitors (e.g. tacrolimus and cyclosporin) are the main culprits.While the main action of calcineurin inhibitors in inducing diabetes is by reducing insulin secretion by pancreatic beta cells, these drugs may also increase insulin resistance . There is good evidence to suggest that there is greater potential of tacrolimus to induce diabetes compared with cyclosporine . Diabetes induced by these drugs may be permanent due to beta-cell destruction, or may only occur while the drug is being taken, with recovery between treatment cycles .
Studies involving other immunosuppressive agents such as mycophenolate mofetil and sirolimus are few and results are inconsistent. Clinical studies have shown that daclizumab seems to have a neutral effect . Patients receiving interferon alpha have been reported to develop diabetes associated with islet cell autoantibodies and, in certain instances, severe insulin deficiency .
There are also many drugs and hormones that can impair insulin action. The list shown in Table 1.3 is not all-inclusive, but reflects the more commonly recognized drug-, hormone-, or toxin-induced forms of diabetes and hyperglycemia. Among these, there are several commonly used diabetes-inducing drugs that deserve special mention. These include the HMG CoA reductase agents (statins), glucocortocoid steroids, anti-HIV agents and antipsychotic drugs.
HMG CoA reductase agents
HMGCoA reductase agents (statins) are commonly used drugs which have been purported to cause diabetes. Sattar et al.  reported that statin use compared to placebo increased risk of diabetes in a meta-analysis of 13 placebo-controlled trials. Anothermeta-analysis comparing intensive dose statin use with moderate statin therapy in five trials showed that the risk of developing diabetes was greater at higher statin doses . The mechanism as to how statins cause diabetes is not known, but it has been suggested that these drugs may affect muscle and liver insulin sensitivity resulting in an increased diabetes risk . It has also been suggested that the observed relationship between statins and diabetes is due to confounding as there is a tendency of individuals who take statins to have a high inherent risk of diabetes. Despite the increased risk of diabetes associated with statin use, a risk–benefit analysis has shown the beneficial nature of statins for cardiovascular disease (CVD), which outweighs the risk of diabetes associated with statin use .
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