DM classification and diagnosis

The American Diabetes Association (ADA) Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021:

1. "Type 1 diabetes (due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency, including latent autoimmune diabetes of adulthood)

2. Type 2 diabetes (due to a progressive loss of adequate β-cell insulin secretion frequently on the background of insulin resistance)

3. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young), diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), and drug- or chemical-induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AIDS, or after organ transplantation)

4. Gestational diabetes mellitus (diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation"

Type 1 diabetes (T1DM) is characterized by an absolute lack or severe deficiency of the pancreatic hormone insulin. Most cases of T1DM are the result of an autoimmune disorder that destroys the insulin-producing beta cells (β-cell) located in the Islets of Langerhans within the pancreas. The loss of endogenous insulin requires exogenous insulin replacement to manage glucose homeostasis. The precipitating cause of the autoimmune disorder remains unknown, but the CDC has cited some predisposing factors in the National Diabetes Statistics Report 2020.

• Geography - T1DM prevalence decreases toward the equator.
• Ancestry - In the U.S., Caucasians bear higher risk of T1DM, African-Americans and Hispanic-Americans to a lesser degree and Chinese-Americans even less
• Genetic variants within the human leukocyte antigen complex (HLA) on Chromosome 6, including the HLA-DQA1, HLA-DQB1, and HLA-DRB1 genes, increase the risk for developing T1DM (see Diabetes diagnostic tests)
• Age; initial diagnosis occurs more often in childhood or adolescents but can occur at any age
• Family history of T1DM increases risk
• Diet - consuming cow's milk at very young age may increase risk
• Viral infections, including German measles, coxsackie, and mumps
• History of other autoimmune disorder: Graves disease, multiple sclerosis and pernicious anemia.

Latent Autoimmune Diabetes in Adults (LADA) diabetes is also known as “late-onset” diabetes and is sometimes referred to as type 1.5 diabetes. Like T1DM, the etiology is immune mediated β-cell destruction which leads to insulin deficiency, but unlike T1DM, it progresses slowly and is often misdiagnosed as T2DM (See table). Many LADA patients are initially treated with oral anti-diabetic medications, but eventually, the pancreas stops producing insulin. This can take anywhere from a few months after diagnosis to several years. Like T1DM, exogenous insulin is required. (https://beyondtype1.org/what-is-lada-diabetes/).

Type 2 diabetes (T2DM) is characterized by progressive insulin resistance, decreased insulin secretion, and decreased suppression of hepatic glucose production. Initially, T2DM is usually treated by lifestyle modification and oral agents like metformin, however, less than 40% of T2DM patients are able to maintain an A1C of <7. Progressive β-cell failure often requires the addition of insulin therapy to avoid prolonged hyperglycemia which can cause glucose toxicity, a potentially reversible impairment in glucose-stimulated insulin secretion. Insulin resistance is usually associated with obesity or older age, the muscle or adipose cells do not respond adequately to normal levels of insulin produced by intact beta-cells. (Van Belle, 2011).  Onset of T2DM symptoms may be gradual or sudden. The symptoms of T2DM include unexplained weight loss, excessive thirst or hunger, fatigue, frequent urination, blurred vision and sometimes nausea and vomiting.

Gestational diabetes

Gestational diabetes is associated with: elevated placental lactogen, T1DM, maternal malnutrition, multiple pregnancies, and fetal macrosomia (Sibiak R. 2020). Risk factors for gestational diabetes include a family history of diabetes, overweight, or over 25 years old. Women who are African American, Hispanic, American Indian or Asian are more likely to develop gestational diabetes (UCSF).

The CDC reports that 2% to 10% of pregnancies in the United States are affected by gestational diabetes.  Once the pregnancy is over the gestational diabetes usually resolves and blood sugars return to normal. However, about 50% of women with gestational diabetes go on to develop T2DM and the child has increased risk of T2DM later in life (CDC).

Routine screening for gestational diabetes is usually done during weeks 24-28 unless risk factors are present making it necessary to screen earlier (UCSF). Once the pregnancy is over the gestational diabetes usually resolves and blood sugars return to normal.

Insulin requirements for pregnant women with pre-existing T1DM gradually increase during the second and third trimesters of pregnancy.

Pre-diabetes is a significant hyperglycemic condition affecting more than 1 in 3 Americans. About 84% of those persons are unaware of that they are at risk for disease progression to T2DM. Risks factors associated with pre-diabetes may include:

• Being overweight
  
• Being 45 years or older
  
• Having a parent, brother, or sister with type 2 diabetes
  
• Being physically active less than 3 times a week
  
• Ever having gestational diabetes (diabetes during pregnancy) or giving birth to a baby who weighed more than 9 pounds
  
• Having polycystic ovary syndrome
  
• Race and ethnicity are also a factor: African Americans, Hispanic/Latino Americans, American Indians, Pacific Islanders, and some Asian Americans are at higher risk (CDC, 2020)

References

American Diabetes Association. Diabetes Care. Standards of Medical Care in Diabetes—2021 Jan; 44(Supplement 1): S15-S33.

Centers for Disease Control and Prevention (2020) Prediabetes. Available from: https://www.cdc.gov/diabetes/basics/prediabetes.html

Dongmei M., Guyer K.M., Dong F., Jiang L., Steck A.K., Rewers M., Eisenbarth G.S., Yu L. (2013) GAD65 Autoantibodies Detected by Electrochemiluminescence Assay Identify High Risk for Type 1 Diabetes. Diabetes. 2013;62(12):4174-4178

National Diabetes Statistics Report 2020.  Available online https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf

O'Neal, K. S., Johnson, J. L., & Panak, R. L. (2016). Recognizing and Appropriately Treating Latent Autoimmune Diabetes in Adults. Diabetes spectrum : a publication of the American Diabetes Association, 29(4), 249–252. https://doi.org/10.2337/ds15-0047

Pieralice, S. & Pozzilli, P. (2018). Latent Autoimmune Diabetes in Adults: A Review on Clinical Implications and Management. Diabetes Metab J. 42(6),451-464. https://doi.org/10.4093/dmj.2018.0190

Sibiak, R., Jankowski, M., Gutaj, P., Mozdziak, P., Kempisty, B., & Wender-Ożegowska, E. (2020). Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives. Journal of clinical medicine, 9(4), 1142. https://doi.org/10.3390/jcm9041142

UCSF (2020) Gestational Diabetes. Diabetes Education Online. Diabetes Teaching Center at the University of California, San Francisco.  Available online: https://dtc.ucsf.edu/types-of-diabetes/gestational-diabetes/