LADA: Not Your Typical Type 2 Diabetes

Most health care providers arefamiliar with type 1 and type 2diabetes mellitus (DM), butthere is another type of diabetes knownas latent autoimmune diabetes in adults(LADA) that is not as well-known orunderstood. LADA is sometimes referredto as type 1½ diabetes because itexhibits characteristics of both type 1and type 2 DM. Type 1 DM is characterizedby an autoimmune destruction ofbeta cells within the pancreas, resultingin little or no insulin production. Type 2DM is not immune-mediated and ischaracterized by inadequate insulinsecretion and resistance to insulin. Asubset of adult patients diagnosed withdiabetes, usually over age 30, are initiallynon-insulin-requiring but progressmore rapidly to insulin dependence andtest positive for islet cell antibodies,usually to glutamic acid decarboxylase(GAD) antibody. This group of patients isidentified as having LADA.

Diagnosing them appropriately andearly is important because of the high riskof rapid progression to insulin dependence.Currently, however, no guidelinesare available to recommend which adultpatients diagnosed with diabetes shouldreceive testing for LADA. A recent 2-partstudy by Fourlanos et al was published inDiabetes Care (May 2006, Vol 29, No 5,pages 970-975) that introduces a clinicalscreening tool to identify which patientsmay benefit from early testing for LADA.After interviewing 213 diabetic patientswho fell into 1 of 2 groups—either positiveor negative for GAD antibodies—they compiled a list of clinical featuresthat were "significantly more frequent" inthe positive GAD group than the negativeGAD group.

Five clinical features were identified inthe group of patients with LADA:

• Age of onset <50 years old
• Acute symptom presentation (polydipsia,polyuria, unintentional weightloss)
• Body mass index (BMI) <25
• Personal history of autoimmune disease
• Family history of autoimmune disease(usually type 1 DM or thyroiddisease)

The majority of LADA patients withinthe study exhibited at least 2 of theabove features. A prospective studywas then conducted that included interviewswith 130 newly diagnosed diabetespatients who did not requireinsulin therapy. GAD antibodies weremeasured, and an LADA risk score wascalculated on each patient according tothe 5 distinguishing clinical factors identifiedin the retrospective study. Afteranalysis, it was confirmed that 4 of the5 features were independently associatedwith the diagnosis of LADA—age ofonset <50, acute symptoms, BMI <25,and personal history of autoimmunedisease. The study conductors determinedthat most patients diagnosedwith LADA have at least 2 of the 5 clinicalfeatures. The median age in theLADA group was 46.2, versus 60.8 yearsin the type 2 diabetes patients. Themost common personal autoimmunedisorder was autoimmune thyroid disorder,and the most common autoimmunedisorder found in patients' relativeswas type 1 DM.

Another small study has shown thatLADA patients typically had high triglyceridelevels (>150 mg/dL) and low highdensitylipoprotein cholesterol levels(<45 mg/dL), which are common parametersin insulin-resistant patients. Italso showed that only 51.4% of thepatients with type 1 DM had C-peptidelevels above 0.3 nmol/L, but 100% of theLADA patients did.

For the most part, LADA is still treatedinitially like type 2 DM. Insulin secretagogues,such as sulfonylureas andmeglitinides, and insulin sensitizers,such as glitazones and metformin, areall reasonable initial choices for therapy.Given the more rapid progression toinsulin dependence than patients withtraditional type 2 DM, early interventionwith medications that preserve beta cellfunction is of utmost importance inthese patients. Therefore, it may be reasonableto consider early use of glitazonesor exenatide since they havebeen shown to preserve endogenousinsulin secretion. As stated earlier, LADApatients will need much earlier treatmentwith insulin than patients with traditionaltype 2 DM. Choice of insulintype should be based on patient-specificparameters but will most likelyrequire both basal and prandial insulincoverage eventually.

Community pharmacists in particularare in an ideal situation to educate anddiscuss the specifics of LADA withpatients who will likely be confused bythis diagnosis. Key educational pointswill be helping patients understand thedifferences between this type of diabetesand traditional type 2 DM andtheir treatment options. More studiesare ongoing about LADA, so as moreinformation becomes available, treatmentoptions may expand as well.

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

For a list of suggested reading, send astamped, self-addressed envelope to: ReferencesDepartment, Attn. A. Rybovic, PharmacyTimes, Ascend Media Healthcare, 103 CollegeRoad East, Princeton, NJ 08540; or send ane-mail request to: arybovic@ascendmedia.com