Pelvic Floor Disorders, Diabetes Mellitus, and Obesity in Women: Findings from the KP CARES Study

Objective: We examined associations between obesity, diabetes mellitus, and female pelvic floor disorders (PFD); stress urinary incontinence (SUI), overactive bladder (OAB), and anal incontinence (AI); in community dwelling women Research Design & Methods: Women were screened for PFD using a validated mailed survey. Diabetes status, glycemic control, and diabetes treatment were extracted from clinical databases while other risk factors for PFD were obtained through self-report. Women were categorized hierarchically as non-obese/non-diabetic (reference); non-obese/diabetic; obese/non-diabetic; and obese/diabetic. Results: Of 3,962 women, 393 (10%) had diabetes. In unadjusted analyses, women with diabetes and women who were obese had greater odds of having each PFD. Among women with diabetes, being obese was associated with SUI and OAB. After adjusting for confounders, we found that obese/diabetic women were at the highest likelihood of having SUI (odds ratio [OR] 95% confidence interval (CI) 3.67; 2.48-5.43) and AI (OR 2.09; 1.48, 2.97). The odds of having OAB among obese women was the same for obese/diabetic women (OR 2.97; 2.08, 4.36) and obese/non-diabetic women (OR 2.93; 2.33, 3.68). Non-obese/diabetic women had higher odds of SUI (OR 1.90, 1.15, 3.11) but did not differ significantly in their OAB (OR 1.45; 0.88, 2.38) and AI (OR 1.33; 0.89, 2.00) prevalence from non-obese/non-diabetic women. Conclusions: Given the impaired quality of life experienced by women with PFDs, health care providers should counsel women that obesity and diabetes may be independent modifiable risk factors for PFD. Pelvic Floor Disorders, Diabetes, and Obesity 3 Diabetes mellitus, obesity, and incontinence are all common health problems for women in the United States. It has been estimated that 9.7 million or 8.8% of all women aged 20 years or older had diabetes in 2005 (1) while almost 50% may experience urinary incontinence in their lifetime (2). In 20032004, 28.6% of women were overweight and 33.2% were obese (3). Urinary incontinence alone accounts for the expenditure of up to 19.5 billion dollars annually in the US (4) and can have a significant impact on the quality of women’s lives (5). Studies have demonstrated the association between urinary incontinence and diabetes (6-12) and some have found that women who used insulin were more likely to be incontinent than women with diabetes that did not require insulin (11-12) but the mechanisms are unclear. It has been suggested that the most likely reason for the increase in risk is microvascular compromise; leading to damage to the urethral sphincter mechanism and bladder sensitivity, and that stricter glycemic control may reduce the risk or severity of urinary incontinence (13). Studies of the relationship between anal incontinence and diabetes have had conflicting results (14, 15). Strong associations between obesity and both urinary and fecal incontinence have been reported (16-24). The pathophysiologic basis posited for this relationship lies in the significant correlation between BMI and intra-abdominal pressure, suggesting that obesity may stress the pelvic floor secondary to a chronic state of increased pressure (25). Weight loss has been shown to improve incontinence in obese women (26-28). In this secondary analysis of data from the KP CARES study, we examined associations between female pelvic floor disorders (PFD) (stress urinary incontinence [SUI], overactive bladder [OAB], and anal incontinence [AI]); diabetes mellitus, and obesity. Pelvic organ prolapse (POP) was excluded from these analyses due to insufficient power to assess the associations of interest for this condition. We sought to evaluate the relative importance of the associations between diabetes and obesity in their contributions to PFDs. RESEARCH DESIGN AND METHODS Study Population and Design Kaiser Permanente is a large pre-paid managed health care plan that serves over three million residents in southern California. The Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ) was developed to assess the prevalence of PFDs in a sample of women from this racially and ethnically diverse population. Survey development, pilot testing, and survey methods have been described elsewhere (29-31). Briefly, the EPIQ was developed and validated in English and Spanish to assess the presence or absence of AI, OAB, SUI, and POP in a community dwelling population. After approval by the Institutional Review Board, samples of 3,050 women in each of four age strata; 25-39 years, 40-54 years, 55-69 years, and 70-84 years were selected from the Kaiser Permanente Southern California (KPSC) membership who had an address on file with the health plan. Surveys in English and Spanish were mailed with a cover letter, small incentive, postcard to opt-out or request additional information, followed by a second survey mailing and a reminder telephone call, and a third survey mailing to women in the youngest age strata (31). Of the 12,200 surveys mailed, 4458 (37%) were returned. Data were collected from April 2004 through January 2005 Pelvic Floor Disorders, Diabetes, and Obesity 4 Assessment of Pelvic Floor Disorders Women were screened for PFDs based on their responses to stem questions plus their degrees of bother as indicated on a visual analog scale. Positive and negative predictive values and 95% confidence intervals for the detection of specific PFDs were: 88% (75-95%) and 87% (76-93%) for SUI, 77% (59-88%) and 90% (81-95%) for OAB, and 61% (48-73%) and 91% (8096%) for AI, respectively. AI included flatal, solid and/or liquid incontinence (30). Assessment of Diabetes Mellitus, Treatment, and Complications We linked survey respondents to the KPSC Diabetes Case Identification Database, which uses an algorithm to identify members who have a high probability of having diabetes (32, 33) based on at least one of the following criteria: 250.XX ICD-9 hospital diagnosis; a prescription for insulin or other oral hypoglycemic agents; or HbA1 ≥ 6.7% or a fructosamine test result ≥ 280 micromol/L. Women with gestational diabetes mellitus (ICD-9 code 648.8) and no other criteria are not included. For this analysis, women who were identified as having diabetes based only on the HbA1c threshold had to meet or exceed 7.0% to increase the sensitivity of the algorithm. We assumed that the majority of these women have Type 2 diabetes as it comprises 8595% of all adults with diabetes (34). To characterize the women with diabetes, information about current treatment (insulin and/or oral hypoglycemic agents) based on the most recent prescription(s) filled prior to survey completion and the results of the HbA1c measured closest to the time of survey completion (± 6 months) were extracted from the pharmacy and laboratory databases, respectively. All laboratory tests were conducted at a single laboratory operated by KPSC. Self-Reported Variables Age was calculated in completed years on the date of survey completion, BMI was calculated as weight in kilograms divided by the square of the height in meters and dichotomized into nonobese (< 30 kg/m) or obese (≥ 30 kg/m). Smoking was categorized as never smoked, past smoker or current smoker. Chronic lifting was defined as repetitive lifting of more than 9 kg regularly for more than one year. Caffeine consumption was defined as more than one cup of caffeinated beverage per day. Presence or absence of neurological disease, lung disease or asthma, history of depression, hysterectomy, menopause status (yes/no/don’t know), and hormone exposure (never/past/present) were assessed using survey data To adjust for the known associations between pregnancy, mode of delivery and PFD as previously described (31), we defined the nulliparous group as those women who had never been pregnant or only delivered a baby less than or equal to 2 kg. The cesarean birth group was defined as having been delivered by one or more cesarean births and no vaginal births exceeding 2 kg. Vaginally parous women were defined as having one or more vaginal deliveries exceeding 2 kg birth weight regardless of history of cesarean births. Parity was modeled as a continuous variable. Statistical Analysis Of the 4,458 EPIQ surveys returned, we excluded women sequentially for the following reasons: insufficient data to categorize into one of the three birth groups (n=289), insufficient information to assess at least one of the PFD (n=66), and insufficient information to calculate BMI (n=141) for a final sample size of 3,962 subjects. Statistical analyses were performed with SAS version 8.02 (SAS Institute, Cary, NC). Power and sample size calculations were based on the primary study objectives, to assess the Pelvic Floor Disorders, Diabetes, and Obesity 5 prevalence of each PFD and identify the risk of vaginal delivery compared to cesarean births (31). We assessed the differences between groups of women using chi-squared tests for categorical variables and student’s t-tests for continuous variables. Each PFD (SUI, OAB, AI) was expressed dichotomously as ‘present’ or ‘absent’. Women for whom we did not have information to assess the presence or absence were excluded from the models for that outcome. Among women with information to assess the presence or absence of at least one of these PFDs, we created a summary variable labeled “any PFD”. Significance was evaluated using a two-sided p-value of less than 0.05. Logistic regression analysis was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the associations between diabetes, obesity and each and any PFD. Multiple logistic regression models were constructed for all women in the study sample. We assessed the contributions of diabetes and obesity to the likelihood of having each and any PFD after controlling for other known risk factors. Women were categorized hierarchically as non-obese/nondiabetic (reference); non-obese/diabetic; obese/non-diabetic; and obese/diabetic. Once all of the variables were entered into the model, we removed covariates that were no longer significant in the multivariate model and had no impact on the primary variable of interest except for age (modeled as a continuous variable), race/ethnicity, mode of delivery, and parity which remained in every model. RESULTS Characteristics of the Study Population by Diabetes Status The median age of the women studied was 56.6 years and the racial/ethnic distribution was 62% White, 19% Hispanic, 10% Black and 8% Asian/Pacific Islanders, and 1% other or unknown race (Table 1). Ten percent (n= 393) of the women in the sample had diabetes. Compared to women without diabetes, we found that women with diabetes were significantly more likely to be older, African American or Hispanic, obese, parous, postmenopausal and to have a hysterectomy, a history of depression, a neurological condition, or lung disease. The prevalence of the PFDs was 15% SUI, 13% OAB, 25% AI, and 35% had any PFD (Table 2). Prevalence of PFDs among Women with Diabetes Women with diabetes were significantly more likely to have each or any PFD than women without diabetes (Table 2). Of the women with diabetes, over half (56%) were obese; 17% were on insulin, 63% were treated with oral hypoglycemic agents only, and 20% were not on any diabetes medications. Over two-thirds (n=271) had an HbA1c test in the six months before or after their survey completion, with a mean value of 7.0%. Of these women, 24% were in borderline control (7.0-8.5%) and 12% were in poor control (> 8.5%). Women with diabetes were 90% more likely to have SUI or OAB, 50% more likely to have AI and 68% more likely to have any PFD than women without diabetes (Table 3). Women with Obesity and Prevalence of PFDs Obese women were over twice as likely to experience SUI and OAB, over 40% more likely to have AI, and 92% more likely to have any PFD than women who were not obese (Table 3). When we restricted our analysis to women with diabetes, as shown at the bottom of Table 3, we found that being obese was positively associated with all conditions, but the relationship with AI was not significant. Pelvic Floor Disorders, Diabetes, and Obesity 6 Other Risk Factors Associated with PFDs under Study When we examined the associations between other common risk factors for PFD, shown in Table 1, and each and any PFD, we found that age, race/ethnicity, smoking status, mode of delivery, parity, hormone use, menopause, previous hysterectomy, history of depression, neurological disease, lung disease, and caffeine consumption were significantly associated with each and any PFD with the following exception – caffeine consumption were not associated with OAB (data not shown). Unadjusted and Adjusted Odds Ratios for Contributions of Diabetes and Obesity When diabetes and obesity were combined hierarchically into a four-category exposure variable; non-obese/non-diabetic (reference); non-obese/diabetic; obese/nondiabetic; and obese/diabetic; we found that the unadjusted odds of having SUI, OAB, AI, or any PFD progressively increased with each category (Table 3). There was no statistical interaction between having diabetes and being obese for any of the four outcomes (data not shown). After controlling for age, race/ethnicity, mode of delivery, and other known risk factors for PFDs that were significant in the bivariate analysis, we found that women categorized as obese/diabetic had the highest probability of having SUI, AI, and any PFD, whereas women who were obese/nondiabetic were as likely as obese/diabetic women to have OAB (Table 4). Women categorized as non-obese/diabetic did not differ significantly in their prevalence of OAB, AI, or any condition than nonobese/non-diabetic women (reference), whereas non-obese/diabetic women were significantly more likely to have SUI than non-obese/non-diabetic women. CONCLUSIONS In our sample of community dwelling women, we found that being obese, regardless of having diabetes, increased the likelihood of having a PFD compared with non-obese women. The prevalence of SUI, AI, and any PFD increased in the following manner: non-obese/nondiabetic (lowest), non-obese/diabetic, obese/non-diabetic, and obese/diabetic (highest), while women who were obese, regardless of whether or not they had diabetes, were most likely to have OAB. Our approach to these analyses differed from others as we directly examined the associations between PDFs and diabetes with or without obesity using women with neither condition as the reference group instead of examining the association between one of these conditions while controlling for the other (9-11). We were able to examine these associations across three different conditions whereas many papers limit their analysis to one condition (7, 9, 10, 12, 28) and, unlike some studies (7, 12) we were able to include pre-menopausal women in our cohort. As with most other studies, we found an association between PFDs and both diabetes and obesity While studies of the relationship between anal incontinence and diabetes have had conflicting results (14, 15), we found that AI was associated with having diabetes among obese women only whereas the relationship between AI and diabetes in women who were not obese was not statistically significant. The strength of this study includes using a carefully validated instrument to assess a spectrum of PFDs in a large, racially and ethnically diverse population distributed across a wide age range include obese and non-obese women. In addition, we were able to characterize the women in our sample with diabetes by linking clinical information about Pelvic Floor Disorders, Diabetes, and Obesity 7 glycemic control and diabetes treatment regimen to the survey responses closest to the time of the survey. Our response rate was lower than anticipated despite considerable effort to increase it, particularly among younger health plan members. We found that younger members were hardest to reach; the likelihood of not having a valid address on file increased with age, from 3% of 70 to 84 year olds to 11% of 25 to 39 year olds. When we compared women in the final analytic sample (n=3,962) to all other women originally surveyed (n=8,238), 10% of the women in the sample and 11% of the remaining women had diabetes (p < 0.05). Among women with diabetes, there was no difference in mean HbA1c percent (p=0.76) nor a difference in the racial/ethnic distribution (p=0.26) when women in the analytic sample were compared to all others originally surveyed. Data on the prevalence of obesity were not available for comparison. Given that our overall prevalence of obesity and diabetes was consistent with what we would have anticipated given national estimates, we do not believe that our response rate biased the result of this study. As this was a secondary analysis of data gathered primarily to evaluate the associations between pregnancy, mode of delivery, and PFD (31), we did not have enough power to assess the relationship between glycemic control, diabetes treatment, and PFDs. Finally, we could only examine associations between prevalent PFDs, obesity, and diabetes without information on the temporal sequence the onset of these conditions since this was a cross-sectional study. The findings from this study suggest that being obese may be a modifiable risk factor for PFD. Women who are obese, regardless of whether they have diabetes, are more likely to have SUI, OAB, and AI whereas non-obese/diabetic women had similar odds of each and any PFD as non-obese/non-diabetic women. Other published studies have suggested that weight loss may reduce the prevalence of incontinence among this group of high risk women. Given the aging of the population, the increased prevalence of obesity, and the concurrent increase in the prevalence of diabetes in the United States, women and health care professionals should be made aware of the associations between PFDs, obesity, and diabetes. Women who are obese, regardless of whether they have diabetes, should be advised that they may be more likely to develop a PFD associated with their weight and should be encouraged to adopt patterns of physical activity and dietary intake to promote healthy weight loss and maintenance of a healthy weight. ACKNOWLEDGEMENTS This study was funded by R01 HD41113. Analyses were funded by Kaiser Permanente Direct Community Benefit funds. The authors acknowledge the contribution of Richard Contreras, Stephen Derose, and Vicki Chiu. Preliminary findings were presented at the American Diabetes Association Annual Meeting in Washington DC, June 9-13, 2006. Pelvic Floor Disorders, Diabetes, and Obesity 8