Prospective studies of muscle capillary basement membrane width in prediabetics

In 1968, this laboratory reported that muscle capillary basement membrane thickening was present in approximately 50% of nondiabetic individuals who had a strong genetic predisposition for developing diabetes mellitus. In the present manuscript we report the 20-yr follow-up observations in this group of prediabetics. We were able to obtain information regarding the presence or absence of diabetes in 17 of 33 subjects (51.5%). In these 17 individuals, 8 (47%) developed diabetes over the ensuing 20+ yr of observation. Initial (1964) glucose tolerance tests in the subjects that developed diabetes were not significantly different from those that did not develop diabetes. One- and 2-h glucose values on follow-up (4-8 yr later) glucose tolerance tests were significantly higher in the group that developed diabetes. On initial biopsy, muscle capillary basement membrane width was similar in the 2 groups; in the follow-up specimens the mean muscle capillary basement membrane width tended to be greater in the group that ultimately developed diabetes, but this difference was not statistically significant. However, in the group that developed diabetes the follow-up muscle capillary basement membrane width increased significantly compared to the initial measurement, whereas in the nondiabetic group the muscle capillary basement membrane width decreased with time (diabetics, +75.50 +/- 23.66; nondiabetic, -14.44 +/- 28.71 A/yr; P less than 0.05). Seven of 8 (87%) of the individuals who developed diabetes showed progressive thickening of their muscle capillary basement membrane thickness, whereas in the nondiabetic group 5 of 8 had a decrease in width. These results suggest that an increase in muscle capillary basement membrane width over time might serve as a marker to detect individuals who are at increased risk to develop diabetes. The detection of an increased susceptibility for diabetes could potentially allow for interventions that could delay or prevent the development of diabetes.