Of the 1442 laboratory studies performed, DM2 patients had 359 [24.9%] abnormal laboratory values. Forty-three of the 68 types of laboratory studies had values from fifteen or more different DM2 patients (representing 1271 total studies). For these forty-three different types of laboratory test, 312 of the 1271 studies [24.5%] were outside of their standard reference range. Tests with responses from fifteen or more patients are listed in in order from highest to lowest percentage of total abnormal values. For each laboratory test listed, the reference range is included in addition to the mean DM2 value, standard deviation, total number of DM2 patients studied, and number (and percentage) of abnormal values from tested DM2 patients. Tests with responses from fewer than fifteen patients are listed in Supplemental Table 1
All together, 10 laboratory tests from had abnormal values in more than 40% of DM2 patients tested. These tests included the levels of creatine kinase (CK), IgG, total cholesterol, lactate dehydrogenase (LD), alanine aminotransferase (ALT), creatinine, serum glucose, total protein, and the absolute lymphocyte and absolute basophil counts. For some studies, the DM2 values were consistently high (i.e., CK, total cholesterol, and ALT levels), whereas other studies demonstrated frequent low values (i.e., IgG, creatinine, and total protein levels). Still other studies had both abnormally high and low values (i.e., serum glucose level).
Certain laboratory tests showed no abnormalities. These included potassium, sodium, total bilirubin and IgA.
The tabulated data add to previous clinical reports of abnormal laboratory values in DM2. Before this study, the two most commonly reported DM2 laboratory values were creatine kinase and gamma-glutamyltransferase (GGT). In one of the initial clinical descriptions of DM2 (then called proximal myotonic myopathy), 18 of 26 patients [69%] had elevated creatine kinase levels and 14 of 18 patients [78%] had higher GGT levels then their stated reference range.(6
) Similarly, Day et al observed that 90% of DM2 patients had elevated CK levels, and 64% had elevated GGT levels. In a population of Italian and American families with DM2, Meola and Moxley reported that 60% of their patients had elevations in CK levels and 58% had increased GGT levels.(7
) Although the present study demonstrated a similar elevation in CK levels (31 of 40 patients tested [78%]), only 33% of the patients had elevations in their GGT levels. Compared to a similarly studied myotonic dystrophy type-1 (DM1) population, on average, the present DM2 patients had higher CK levels (DM2: 537 u/L; DM1: 183 u/L) and lower GGT levels (DM2: 61.1 u/L; DM1: 110.4 u/L). (5
In 2003, Day et al observed that 29% of patients with DM2 had low testosterone levels, 65% had high follicle-stimulation hormone levels, and 75% had insulin insensitivity (elevated basal insulin levels or prolonged insulin elevation).(3
) Decreased levels of luteinizing hormone have also been reported.(8
) Although endocrinologic laboratory sampling was limited in this study, we found similar trends in this population. Five of twelve patients had elevated follicle-stimulation hormone levels and one of eleven had a low level of luteinizing hormone. In seven patients who had their testosterone tested, one had a low level and three had values higher than the standard reference range. It is unknown, however, whether any of these patient were taking testosterone supplementation at the time of testing. Although none of the present patients had basal insulin level testing, 9 of 30 [30%] had baseline serum glucose elevations.
An association between autoimmune laboratory dysfunction and DM2 has been previously hypothesized.(9
) Day et al reported that although DM2 patients have normal IgA levels, 65% have low IgG levels and 11% have low IgM levels.(3
) Similarly, 17 of the present DM2 patients had normal IgA levels, 12 of 16 [75%] had low IgG levels, and 2 of 17 [12%] had low IgM levels. We also found that 5 of 14 [36%] had elevations in their IgE values.
In a 2006 Archives of Neurology
article we detailed the laboratory abnormalities of myotonic dystrophy type-1 (DM1).(5
) Despite the genetic differences between DM1 and DM2, many similarities were noted between the laboratory profiles of these conditions. Both populations were found to have elevated serum cholesterol levels, increased liver and muscle markers, decreases in select hematologic counts, reductions in nutritional markers, and relatively preserved electrolyte studies. Despite these similarities the mean values, and percentage of abnormal values for each study varied per population for each individual test. Several factors may have played a role in this, including but not limited to: 1) the inclusion criteria for the DM1 and DM2 study patients (our previous DM1 population was selected only from ambulatory, mild to moderately affected individuals); 2) the mild variation in laboratory techniques and reference values over time; and, 3) the underlying varying pathomechanisms of these two diseases.