Is type 2 diabetes a chronic inflammatory/autoimmune disease?

The classification of diabetes mellitus into 2 main types, defined as Type 1 and 2 diabetes (T1DM, T2DM) relies mostly on the requirement of insulin therapy and on the presence of detectable immunologic abnormalities. However, this distinction is far from straightforward and there is considerable overlap between these 2 types of diabetes. Islet cell autoimmunity, which is characteristic of T1DM, appears in fact to be present in up to 10-15% of subjects diagnosed clinically with T2DM. In the UK Prospective Diabetes Study (UKPDS), it was reported that in patients diagnosed with in T2DM, the presence of autoantibodies to the enzyme glutamic acid decarboxylase (GAD) and cytoplasmic islet cell antibodies (ICA) were a predictor of insulin requirement as compared with patients not carrying these autoantibodies. These results are strikingly similar to a number of prospective studies carried out in childhood diabetes. If islet cell autoimmunity is truly present in 10-15% of subjects clinically diagnosed with T2DM, up to two million Americans might have an unidentified autoimmune form of T2DM, a prevalence similar to that of recent onset childhood diabetes. In addition, we found that in a subset of T2DM patients, a pronounced activation of the acute phase response that seems to be associated with islet cell autoimmunity. These results may in part explain the defect in insulin secretion as well as insulin resistance seen in T2DM. The identification of a subgroup of individuals at risk of developing T2DM using autoantibody as well as inflammatory markers is of public health interest, not only for the correct classification of diabetes, but also because immunomodulatory therapeutic strategies could potentially be instituted sufficiently early in a large number of patients diagnosed as having T2DM and most likely delay the onset of insulin requirement and the complications related with hyperglycemia.

Methicillin-resistant Staphylococcus aureus in U.S. hospitals, 1975-1991.

OBJECTIVES: Analyze changes that have occurred among U.S. hospitals over a 17-year period, 1975 through 1991, in the percentage of Staphylococcus aureus resistant to beta-lactam antibiotics and associated with nosocomial infections. DESIGN: Retrospective review. The percentage of methicillin-resistant S aureus (MRSA) was defined as the number of S aureus isolates resistant to either methicillin, oxacillin, or nafcillin divided by the total number of S aureus isolates for which methicillin, oxacillin, or nafcillin susceptibility test results were reported to the National Nosocomial Infections Surveillance (NNIS) System. SETTING: NNIS System hospitals. RESULTS: Of the 66,132 S aureus isolates that were tested for susceptibility to methicillin, oxacillin, or nafcillin during 1975 through 1991, 6,986 (11%) were resistant to methicillin, oxacillin, or nafcillin. The percentage MRSA among all hospitals rose from 2.4% in 1975 to 29% in 1991, but the rate of increase differed significantly among 3 bed-size categories: < 200 beds, 200 to 499 beds, and > or = 500 beds. In 1991, for hospitals with < 200 beds, 14.9% of S aureus isolates were MRSA; for hospitals with 200 to 499 beds, 20.3% were MRSA; and for hospitals with > or = 500 beds, 38.3% were MRSA. The percentage MRSA in each of the bed-size categories rose above 5% at different times: in 1983, for hospitals with > or = 500 beds; in 1985, for hospitals with 200 to 499 beds; and in 1987, for hospitals with < 200 beds. CONCLUSIONS: This study suggests that hospitals of all sizes are facing the problem of MRSA, the problem appears to be increasing regardless of hospital size, and control measures advocated for MRSA appear to require re-evaluation. Further study of MRSA in hospitals would benefit our understanding of this costly pathogen.

Comparison of rates of nosocomial infections in neonatal intensive care units in the United States. National Nosocomial Infections Surveillance System.

To determine nosocomial infection (NI) rates among neonatal intensive care units (NICUs) that are useful for interhospital comparison, we analyzed data reported in 1986-1990 from 35 hospitals that have level III NICUs and used standard National Nosocomial Infections Surveillance protocols and NI site definitions. Overall rates of NI were calculated as the number of NI per 100 patients (overall NI patient rates) or the number of NI per 1,000 NICU patient-days (overall NI patient-day rates). A strong positive association was found between overall NI patient rates and the neonates' average length of stay, a marker for duration of exposure to important risk factors. No correlation was found between overall NI patient-day rates and average length of stay. However, a strong positive correlation between overall NI patient-day rates and a measure of device utilization (total device-days/total patient-days x 100) was found. Additionally, a positive correlation between overall NI patient rates and device utilization was found. Stratification among the three birthweight groups (less than 1,500 g, 1,500-2,500 g, greater than 2,500 g) did not eliminate the need to control for variations in these factors among NICUs. Device-associated, device-day infection rates, calculated as the number of umbilical or central line-associated blood-stream infections per 1,000 umbilical or central line-days and the number of ventilator-associated pneumonias per 1,000 ventilator days, were not correlated with a unit's site-specific device utilization. These data suggest that calculation of device-associated NI rates in NICUs using device-days as the denominator helps to control for the duration of exposure to the primary risk factor and will be more meaningful for purposes of interhospital comparison.

Nosocomial infections in elderly patients in the United States, 1986-1990. National Nosocomial Infections Surveillance System.

We analyzed 101,479 nosocomial infections in 75,398 adult patients (greater than 15 years) that were reported to the National Nosocomial Infections Surveillance (NNIS) system between 1986 and 1990 by 89 hospitals using the NNIS hospital-wide surveillance component. Overall, 54% of the infections occurred in elderly patients (greater than or equal to 65 years). In the elderly, 44% of the infections were urinary tract infections (UTIs), 18% were pneumonias, 11% were surgical wound infections (SWIs), 8% were bloodstream infections (BSIs), and the remainder were infections at other sites. When we compared the infections in elderly patients with those in younger adult patients, ages 15 to 64 years, a far greater percentage of the infections in elderly patients were UTIs, and there were more pneumonias than SWIs. Elderly and younger patients with ventilator-associated pneumonia were about 1.5 times more likely to develop a secondary BSI than those with pneumonia not associated with ventilator use. When the pathogens isolated from the infections were compared to those reported to the NNIS system in 1984, the percentage that were coagulase-negative staphylococci had increased in both elderly and younger patients. The patient died in 12% of all of the infections. Surveillance personnel reported that 54% of the infections in elderly infected patients who died were related to death compared with 59% in younger infected patients who died. When the infection was related to the patient's death, it was most often pneumonia or a BSI. The risk of an infection-related death was significantly higher when the infected patient developed a secondary BSI. Infection prevention efforts should target infections that occur frequently, are amenable to intervention, and have an adverse outcome.

The National Nosocomial Infections Surveillance System: plans for the 1990s and beyond.

The National Nosocomial Infections Surveillance (NNIS) System is an ongoing collaborative surveillance system among the Centers for Disease Control (CDC) and United States hospitals to obtain national data on nosocomial infections. This system provides comparative data for hospitals and can be used to identify changes in infection sites, risk factors, and pathogens, and develop efficient surveillance methods. Data are collected prospectively using four surveillance components: hospital-wide, intensive care unit, high-risk nursery, and surgical patient. The limitations of NNIS data include the variability in case-finding methods, infrequency or unavailability of culturing, and lack of consistent methods for post-discharge surveillance. Future plans include more routine feedback of data, studies on the validity of NNIS data, new components, a NNIS consultant group, and more rapid data exchange with NNIS hospitals. Increasing the number of NNIS hospitals and cooperating with other agencies to exchange data may allow NNIS data to be used better for generating benchmark nosocomial infection rates. The NNIS system will continue to evolve as it seeks to find more effective and efficient ways to measure the nosocomial infection experience and assess the influence of patient risk, changes in the delivery of hospital care, and changes in infection control practices on these measures.

Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System.

To perform a valid comparison of rates among surgeons, among hospitals, or across time, surgical wound infection (SWI) rates must account for the variation in patients' underlying severity of illness and other important risk factors. From January 1987 through December 1990, 44 National Nosocomial Infections Surveillance System hospitals reported data collected under the detailed option of the surgical patient surveillance component protocol, which includes definitions of eligible patients, operations, and nosocomial infections. Pooled mean SWI rates (number of infections per 100 operations) within each of the categories of the traditional wound classification system were 2.1, 3.3, 6.4, and 7.1, respectively. A risk index was developed to predict a surgical patient's risk of acquiring an SWI. The risk index score, ranging from 0 to 3, is the number of risk factors present among the following: (1) a patient with an American Society of Anesthesiologists preoperative assessment score of 3, 4, or 5, (2) an operation classified as contaminated or dirty-infected, and (3) an operation lasting over T hours, where T depends upon the operative procedure being performed. The SWI rates for patients with scores of 0, 1, 2, and 3 were 1.5, 2.9, 6.8, and 13.0, respectively. The risk index is a significantly better predictor of SWI risk than the traditional wound classification system and performs well across a broad range of operative procedures.

Effect of murine gamma interferon on the cellular responses to bleomycin in mice.

Because in vitro studies have shown inhibition of fibroblast proliferation and collagen synthesis by interferon, we tested the hypothesis that murine gamma interferon inhibits bleomycin-induced pulmonary fibrosis in mice. Mice were divided into the following groups: saline plus vehicle (27), saline plus interferon (29), bleomycin plus vehicle (26), and bleomycin plus interferon (26). Bleomycin or saline were given intratracheally once at the beginning of the experiment and vehicle (phosphate-buffered saline) or interferon was given intramuscularly daily. Mice were killed at 14 or 21 days of the experiment. About half of the mice from each group were used for collagen biochemistry and half for bronchoalveolar lung lavage, transmission electron microscopy (TEM), and morphometry. Hydroxyproline content showed a significant reduction in bleomycin plus interferon compared to bleomycin plus vehicle mice at 21 days. The saline plus vehicle and saline plus interferon mice showed no difference in hydroxyproline content. Similarly, bronchoalveolar lavage showed no differences between saline plus vehicle and saline plus interferon mice; however, all mice treated with bleomycin showed significant increases in total cells as compared to saline treated mice. At 14 and 21 days in bronchoalveolar lavage there were significantly more lymphocytes in bleomycin plus interferon compared to bleomycin plus vehicle mice. In bronchoalveolar lavage, there were usually fewer neutrophils, monocytes and macrophages in bleomycin plus interferon compared to bleomycin plus vehicle mice. Morphometric estimates of the volume of lesion within lung showed no significant differences among the bleomycin treated groups. Stainable collagen fibers were less, but not significantly, in the bleomycin plus interferon compared to bleomycin plus vehicle mice. The number of fibroblasts per volume of lesion was significantly decreased at 14 and 21 days in bleomycin plus interferon compared to bleomycin plus vehicle mice. The total volume of lymphocytes in interstitial lesions was significantly greater at 14 and 21 days in bleomycin plus interferon mice compared to bleomycin plus vehicle mice. These results suggest an inhibitory action of gamma interferon on collagen accumulation and fibroblast proliferation associated with lymphocyte accumulation in the lungs of mice following bleomycin administration.