Type 1 diabetes

Type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic β-cells which typically leads to complete lack of insulin and may include cases of latent autoimmune diabetes in adults (ElSayed et al., 2022). There is variability in the genetic, metabolic and immunogenetic features of type 1 diabetes along with age-related factors; therefore, an individualized approach is needed for each person. The decline in insulin secretion can either be gradual or quick. Adults with type 1 diabetes usually retain some insulin production (detectable/higher c-peptide) whilst youth-onset cases have more prevalent diabetic ketoacidosis. The detection of c-peptide correlates with improved glycemic control. Moreover, the presence of other autoimmune conditions, obesity, comorbidities as well as the onset of diabetes-related complications varies among individuals. Effective management of type 1 diabetes requires the use of multiple daily insulin injections (MDI), insulin pump therapy or automated insulin delivery systems, along with glucose monitoring- preferably through continuous glucose monitoring (CGM). If CGM is not available, all individuals with type 1 diabetes should be capable of performing capillary blood glucose monitoring (BGM). Additionally, optimizing outcomes involves self-management education, training, and support, as well as addressing psychosocial factors all of which can be addressed with a collaborative interprofessional healthcare team (Lucier & Weinstock, 2023). 

Type 2 diabetes

Contrasting Type 1 diabetes, Type 2 diabetes is caused by a non-autoimmune, gradual decline in β-cell insulin secretion, often occurring alongside insulin resistance and metabolic syndrome. Previously known as "non-insulin-dependent diabetes" or "adult-onset diabetes," it makes up around 90–95% of all diabetes cases. This type involves individuals with a relative, rather than absolute, insulin deficiency and peripheral insulin resistance. Initially, and often throughout their lives, these individuals may not require insulin for survival. Type 2 diabetes has diverse causes and there is no autoimmune destruction of pancreatic β-cells, and patients lack other known diabetes causes. Furthermore, most individuals with type 2 diabetes are overweight or obese and excess weight itself induces some level of insulin resistance. Even those that are not obese or overweight in accordance to traditional weight-related criteria may exhibit an increased percentage of body fat, particularly in the abdominal region. Diabetic ketoacidosis rarely manifests in type 2 diabetes and if it is observed, it typically arises in association with the stress of another illness, such as infection or myocardial infarction, or the use of specific medications (e.g., corticosteroids, atypical antipsychotics, and sodium–glucose cotransporter 2 inhibitors). Type 2 diabetes often remains undetected for many years as hyperglycemia develops gradually. In the early stages, hyperglycemia is usually not severe enough for the patient to acknowledge the classic diabetes symptoms it causes, such as dehydration or unintentional weight loss. Despite this, even individuals with undiagnosed diabetes face an elevated risk of developing both macrovascular and microvascular complications. Individuals with type 2 diabetes may exhibit insulin levels that appear normal or elevated, but the inability to regulate blood glucose indicates a relative deficiency in insulin secretion stimulated by glucose. Consequently, insulin secretion is defective and inadequate to counteract insulin resistance. While weight reduction, physical activity, or pharmacological management of hyperglycemia may ameliorate insulin resistance, it is rarely completely restored to normal levels (ElSayed et al., 2022).

Gestational diabetes mellitus

Gestational diabetes mellitus refers to diabetes diagnosed in the second or third trimester of pregnancy, which was not definitively overt diabetes before the onset of gestation. For an extended period, gestational diabetes mellitus (GDM) was defined as any level of glucose intolerance identified for the first-time during pregnancy, regardless of the degree of hyperglycemia. Although this definition streamlined the approach to detecting and categorizing GDM, it has notable drawbacks. Firstly, the best available evidence suggests that numerous instances of GDM indicate preexisting hyperglycemia, which is identified through routine screening during pregnancy, since routine screening is not widely conducted in nonpregnant individuals of reproductive age. The clinical significance stems from the severity of hyperglycemia concerning both short- and long-term risks for the mother and fetus. The escalating prevalence of obesity and diabetes has resulted in a rise in type 2 diabetes among individuals of reproductive age, with an increased number of pregnant individuals with undiagnosed type 2 diabetes in early pregnancy. It is ideal that undiagnosed diabetes should be detected before conception in individuals with risk factors or in high-risk populations (ElSayed et al., 2022).

Monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young)
Monogenic abnormalities leading to β-cell dysfunction constitute a minority of individuals with diabetes, comprising less than 5% of cases (ElSayed et al., 2022).
Diabetes that manifests before the age of 6 months is referred to as "neonatal" or "congenital" diabetes, with approximately 80–85% of cases attributed to an underlying monogenic cause. Neonatal diabetes is less common after the age of 6 months, while autoimmune type 1 diabetes rarely occurs before this age. Neonatal diabetes can be either transient or permanent. Transient diabetes is frequently associated with the overexpression of genes on chromosome 6q24, recurs in about half of cases, and could be treatable with medications other than insulin. Permanent neonatal diabetes is most often caused by autosomal dominant mutations in the genes that encode the Kir6.2 subunit (KCNJ11) and SUR1 subunit (ABCC8) of the β-cell KATP channel. Accurate diagnosis is crucial since 30–50% of individuals with KATP-related neonatal diabetes can experience enhanced blood glucose control with high-dose oral sulfonylureas instead of insulin. Permanent neonatal diabetes, often caused by insulin gene (INS) mutations, is the second most common form. While intensive insulin management is the current preferred treatment, genetic counseling is important to consider since most of the mutations that cause diabetes are dominantly inherited (ElSayed et al., 2022).
Maturity-Onset Diabetes of the Young (MODY) is usually characterized by hyperglycemia onset at an early age, typically before 25 years, though diagnosis can occur later. It is characterized by impaired insulin secretion, with minimal or no issues in insulin secretion, particularly in the absence of coexisting obesity. MODY follows an autosomal dominant inheritance pattern, involving abnormalities in at least 13 genes on different chromosomes. Commonly reported forms include GCK-MODY (MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1). Given the substantial treatment implications for those with MODY, genetic testing is recommended (ElSayed et al., 2022).

Cystic Fibrosis–Related Diabetes

Cystic fibrosis–related diabetes (CFRD) is the most prevalent comorbidity among individuals with cystic fibrosis, affecting approximately 20% of adolescents and 40–50% of adults. In comparison to individuals with type 1 or type 2 diabetes, those with CFRD are associated with poorer nutritional status, more pronounced inflammatory lung disease, and higher mortality rates. The main defect in CFRD is insufficient insulin. Genetic factors influencing β-cell function, along with insulin resistance associated with infection and inflammation, may also contribute to CFRD development. Mild glucose tolerance abnormalities are even more common and manifest at earlier ages than CFRD (Elsayed et al., 2022).

Post transplantation Diabetes Mellitus

Various terms are employed in literature to depict the occurrence of diabetes after organ transplantation. "New-onset diabetes after transplantation" (NODAT) is one such term, referring to individuals developing diabetes post-transplantation. It excludes those with pre-transplant diabetes that went undiagnosed as well as post-transplant hyperglycemia that resolves by the time of discharge. Another term, "post transplantation diabetes mellitus" (PTDM), signifies the presence of diabetes in the post-transplant period, regardless of when diabetes initiated. Hyperglycemia is highly prevalent in the initial post-transplant phase, with around 90% of kidney allograft recipients experiencing it in the first few weeks after transplant. Typically, stress or steroid-induced hyperglycemia resolves by discharge in most cases. While immunosuppressive therapies significantly contribute to post transplantation diabetes mellitus (PTDM) development, the risks of transplant rejection outweigh PTDM risks. The role of diabetes care professionals is to appropriately manage hyperglycemia regardless of the immunosuppression type. Risk factors for PTDM encompass general diabetes risks (e.g., age, family history) and transplant-specific factors like immunosuppressant medications. While post transplantation hyperglycemia is a notable risk for subsequent PTDM, a formal PTDM diagnosis is ideally made when the patient stabilizes on maintenance immunosuppression and is free of acute infection (ElSayed et al., 2022).

Pancreatic Diabetes or Diabetes in the Context of Disease of the Exocrine Pancreas

Pancreatic diabetes encompasses both structural and functional loss of insulin secretion to regulate glucose levels in the context of exocrine pancreatic dysfunction and is often misdiagnosed as type 2 diabetes. Hyperglycemia because of general pancreatic dysfunction has been referred to as "type 3c diabetes" and, more recently, pancreoprivic diabetes in terms of disease of the exocrine pancreas. Various causes include acute and chronic pancreatitis, trauma, pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis, fibro calculous pancreatopathy, rare genetic disorders, and idiopathic forms and hence the umbrella term "pancreatic diabetes" is preferred. Even a single bout of pancreatitis can lead to post pancreatitis diabetes mellitus (PPDM), with both acute and chronic pancreatitis posing a risk, particularly with recurrent episodes. Distinguishing features include concurrent pancreatic exocrine insufficiency, pathological pancreatic imaging, and the absence of type 1 diabetes-associated autoimmunity. There is a loss of both insulin and glucagon secretion, often resulting in higher-than-expected insulin requirements. Microvascular complication risks are comparable to other forms of diabetes (ElSayed et al., 2022).