LADA: Not Your Typical Type 2 Diabetes

DECEMBER 01, 2006
Amy H. Brian, PharmD, CPP, CDE

Most health care providers are familiar with type 1 and type 2 diabetes mellitus (DM), but there is another type of diabetes known as latent autoimmune diabetes in adults (LADA) that is not as well-known or understood. LADA is sometimes referred to as type 1½ diabetes because it exhibits characteristics of both type 1 and type 2 DM. Type 1 DM is characterized by an autoimmune destruction of beta cells within the pancreas, resulting in little or no insulin production. Type 2 DM is not immune-mediated and is characterized by inadequate insulin secretion and resistance to insulin. A subset of adult patients diagnosed with diabetes, usually over age 30, are initially non-insulin-requiring but progress more rapidly to insulin dependence and test positive for islet cell antibodies, usually to glutamic acid decarboxylase (GAD) antibody. This group of patients is identified as having LADA.

Diagnosing them appropriately and early is important because of the high risk of rapid progression to insulin dependence. Currently, however, no guidelines are available to recommend which adult patients diagnosed with diabetes should receive testing for LADA. A recent 2-part study by Fourlanos et al was published in Diabetes Care (May 2006, Vol 29, No 5, pages 970-975) that introduces a clinical screening tool to identify which patients may benefit from early testing for LADA. After interviewing 213 diabetic patients who fell into 1 of 2 groups—either positive or negative for GAD antibodies— they compiled a list of clinical features that were "significantly more frequent" in the positive GAD group than the negative GAD group.

Five clinical features were identified in the group of patients with LADA:

  1. Age of onset <50 years old
  2. Acute symptom presentation (polydipsia, polyuria, unintentional weight loss)
  3. Body mass index (BMI) <25
  4. Personal history of autoimmune disease
  5. Family history of autoimmune disease (usually type 1 DM or thyroid disease)

The majority of LADA patients within the study exhibited at least 2 of the above features. A prospective study was then conducted that included interviews with 130 newly diagnosed diabetes patients who did not require insulin therapy. GAD antibodies were measured, and an LADA risk score was calculated on each patient according to the 5 distinguishing clinical factors identified in the retrospective study. After analysis, it was confirmed that 4 of the 5 features were independently associated with the diagnosis of LADA—age of onset <50, acute symptoms, BMI <25, and personal history of autoimmune disease. The study conductors determined that most patients diagnosed with LADA have at least 2 of the 5 clinical features. The median age in the LADA group was 46.2, versus 60.8 years in the type 2 diabetes patients. The most common personal autoimmune disorder was autoimmune thyroid disorder, and the most common autoimmune disorder found in patients' relatives was type 1 DM.

Another small study has shown that LADA patients typically had high triglyceride levels (>150 mg/dL) and low highdensity lipoprotein cholesterol levels (<45 mg/dL), which are common parameters in insulin-resistant patients. It also showed that only 51.4% of the patients with type 1 DM had C-peptide levels above 0.3 nmol/L, but 100% of the LADA patients did.

For the most part, LADA is still treated initially like type 2 DM. Insulin secretagogues, such as sulfonylureas and meglitinides, and insulin sensitizers, such as glitazones and metformin, are all reasonable initial choices for therapy. Given the more rapid progression to insulin dependence than patients with traditional type 2 DM, early intervention with medications that preserve beta cell function is of utmost importance in these patients. Therefore, it may be reasonable to consider early use of glitazones or exenatide since they have been shown to preserve endogenous insulin secretion. As stated earlier, LADA patients will need much earlier treatment with insulin than patients with traditional type 2 DM. Choice of insulin type should be based on patient-specific parameters but will most likely require both basal and prandial insulin coverage eventually.

Community pharmacists in particular are in an ideal situation to educate and discuss the specifics of LADA with patients who will likely be confused by this diagnosis. Key educational points will be helping patients understand the differences between this type of diabetes and traditional type 2 DM and their treatment options. More studies are ongoing about LADA, so as more information becomes available, treatment options may expand as well.

Dr. Brian is a clinical specialist with Cornerstone Health Care, High Point, NC.

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