Amy G. Huebschmann

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus A Scientific Statement From the American Heart Association

The prevalence of diabetes mellitus (DM) is increasing at a rapid rate. In the United States in 2012, 29.1 million Americans, or 9.3% of the population, had DM.1 Currently, ≈1 in 13 people living in the United States has DM, and 90% to 95% of these individuals have type 2 DM (T2DM).2 Overall, the prevalence of T2DM is similar in women and men. In the United States, ≈12.6 million women (10.8%) and 13 million men (11.8%) ≥20 years of age are currently estimated to have T2DM.2 Among individuals with T2DM, cardiovascular disease (CVD) is the leading cause of morbidity and mortality and accounts for >75% of hospitalizations and >50% of all deaths.3 Although nondiabetic women have fewer cardiovascular events than nondiabetic men of the same age, this advantage appears to be lost in the context of T2DM.4,5 The reasons for this advantage are not entirely clear but are likely multifactorial with contributions from inherent physiological differences, including the impact of the sex hormones, differences in cardiovascular risk factors, and differences between the sexes in the diagnosis and treatment of DM and CVD.6 In addition, there are racial and ethnic factors to consider because women of ethnic minority backgrounds have a higher prevalence of DM than non-Hispanic white (NHW) women. This scientific statement was designed to provide the current state of knowledge about sex differences in the cardiovascular consequences of DM, and it will identify areas that would benefit from further research because much is still unknown about sex differences in DM and CVD. Areas that are discussed include hormonal differences between the sexes and their possible effects on the interaction between DM and CVD, sex differences in epidemiology, ethnic and racial differences and risk factors for CVD in DM across the life …

Women with type 2 diabetes perceive harder effort during exercise than nondiabetic women.

Regular exercise is a cornerstone of diabetes treatment; however, people with type 2 diabetes (T2D) are commonly sedentary. It is possible that a harder rate of perceived exertion (RPE) during exercise for those with T2D as compared with nondiabetics may be a barrier to physical activity. This study examined RPE (Borg scale, ordinal range 6-20) during submaximal exercise at identical absolute work rates to test the hypothesis that women with T2D demonstrate harder RPE during exercise than nondiabetic controls. In a prespecified analysis of existing data from equivalently sedentary women, RPE during submaximal exercise was compared among women with uncomplicated T2D (n = 13, mean body mass index (BMI) 34.2, mean hemoglobin A1c 9%), overweight controls (OC, n = 13, mean BMI 30.7), and normal-weight controls (NWC, n = 13, mean BMI 23.1). Subjects performed three 7 min, constant-load exercise tests at 20 W and 30 W. Mixed-effects general linear modeling was used to test for differences in mean RPE estimates among groups with and without adjustment for relative work intensity, age, habitual physical activity, or BMI. Subjects with T2D perceived harder effort during bicycling exercise than controls, as measured by RPE at 20 W and 30 W (p < 0.05 for T2D vs. OC and for T2D vs. NWC). Adjusting for relative work intensity eliminated significant group RPE differences at 30 W, but group RPE differences at 20 W remained significant. Harder perceived effort during exercise may be a barrier to physical activity for those with T2D.

Sex Differences in the Effects of Type 2 Diabetes on Exercise Performance

PURPOSE People with uncomplicated type 2 diabetes (T2D) have impaired peak exercise performance compared with that of their nondiabetic counterparts. This impairment may represent the earliest indication of cardiovascular (CV) abnormalities in T2D. Women with T2D are known to have worse CV outcomes than those in men with T2D. We hypothesized that women with diabetes have a greater exercise impairment than that in men with diabetes compared with that in their nondiabetic counterparts. METHODS We studied 15 women (premenopausal) and 14 men with T2D as well as their nondiabetic counterparts (22 women and 13 men). Exercise testing was performed. Additional outcomes included measurements of insulin sensitivity, endothelial function, blood flow, and resting cardiac function. RESULTS Men and women with T2D but not controls had impaired insulin sensitivity. Women with T2D had a lower peak oxygen consumption (V˙O2peak) compared with that of nondiabetic women (24%, P < 0.05) than men with diabetes compared with that in nondiabetic men (16%, P < 0.05) (P value between groups < 0.05). The time constants (phase 2) of the V˙O2 kinetic response tended to be slower in men and women with T2D than those in nondiabetic controls (P = 0.08). There were no differences in resting ventricular function by Doppler echocardiography techniques between groups. Women with T2D had significantly lower flow-mediated dilation and blood flow responses to hyperemia than those in nondiabetic women (both P < 0.05), whereas men with T2D had lower flow-mediated dilation but not lower blood flow than those in nondiabetic men. CONCLUSIONS Although both men and women with uncomplicated T2D had a lower V˙O2peak, the abnormality in women with T2D compared with that in nondiabetic women was greater than that seen in men. Because V˙O2peak has a strong inverse correlation with mortality, sex disparities observed in exercise capacity among people with T2D suggest a possible rationale for the increased CV morbidity and mortality observed in women compared with those observed in men with uncomplicated T2D.

Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women

Objective Type 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM. Research design and methods We enrolled overweight, sedentary women aged 50–75 years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30 W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration. Results VO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30 W: Control, 10.4±3.2, T2DM, 11.7±2.3, p=0.08; 35% VO2peak: Control, 11.1±0.5, T2DM, 12.1±0.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30 W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30 W and 35% VO2peak). Conclusions Taken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought. Trial number NCT00785005.

Fear of injury with physical activity is greater in adults with diabetes than in adults without diabetes.

OBJECTIVE Physical activity is a cornerstone of treatment for diabetes, yet people with diabetes perform less moderate and vigorous physical activity (MVPA) than people without diabetes. In contrast, whether differences in walking activity exist has been understudied. Diabetes-specific barriers to physical activity are one possible explanation for lower MVPA in diabetes. We hypothesized that people with diabetes would perform less walking and combined MVPA and would be less likely to anticipate increasing physical activity if barriers were theoretically absent, compared with people without diabetes. RESEARCH DESIGN AND METHODS We surveyed 1,848 randomly selected rural Colorado adult residents by telephone from 2002 to 2004. Respondents reported weekly walking and MVPA duration and their likelihood of increasing physical activity if each of seven barriers was theoretically absent. RESULTS People with diabetes (n = 129) had lower odds of walking and MVPA than people without diabetes (walking: adjusted odds ratio 0.62 [95% CI 0.40–0.95]; MVPA: adjusted odds ratio 0.60 [0.36–0.99]; ≥10 vs. <10 min/week, adjusted for age, sex, BMI, and ethnicity). Respondents with diabetes reported fear of injury as a barrier to physical activity more often than respondents without diabetes (56 vs. 39%; P = 0.0002), although this relationship was attenuated after adjusting for age and BMI (adjusted odds ratio 1.36 [0.93–1.99]). CONCLUSIONS Although walking is a preferred form of activity in diabetes, people with diabetes walk less than people without diabetes. Reducing fear of injury may potentially increase physical activity for people with diabetes, particularly in older and more overweight individuals.

Exercise attenuates the premature cardiovascular aging effects of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2D) is an example of a disease process that results in decrements in function additional to those imposed by the inexorable ‘primary aging’ process. These decrements due to disease, rather than primary aging, can be termed ‘secondary aging’, and include the premature development (as early as adolescence) of asymptomatic preclinical cardiovascular abnormalities (e.g. endothelial dysfunction, arterial stiffness, diastolic dysfunction), as well as impaired exercise performance. These abnormalities are important, as they are associated with greater cardiovascular morbidity and mortality in people with and without T2D. A better understanding of the pathophysiology of secondary cardiovascular aging in people with T2D is warranted, and an evaluation of the benefits of existing treatments for these abnormalities is useful (e.g. exercise training). The focus of this review is to discuss the data relevant to the following key postulates: (a) T2D causes premature cardiovascular aging; (b) in contrast to primary cardiovascular aging, the premature cardiovascular aging of T2D may be modifiable with exercise. The exercise-focused perspective for this review is appropriate because impairments in exercise performance are markers of premature cardiovascular aging in T2D, and also because exercise training shows promise to attenuate some aspects of cardiovascular aging during the preclinical stage.

Missed opportunities for providing low-fat dietary advice to people with diabetes.

Introduction Because cardiovascular disease is closely linked to diabetes, national guidelines recommend low-fat dietary advice for patients who have cardiovascular disease or are at risk for diabetes. The prevalence of receiving such advice is not known. We assessed the lifetime prevalence rates of receiving low-fat dietary advice from a health professional and the relationship between having diabetes or risk factors for diabetes and receiving low-fat dietary advice. Methods From 2002 through 2009, 188,006 adults answered the following question in the Medical Expenditure Panel Survey: “Has a doctor or other health professional ever advised you to eat fewer high-fat or high-cholesterol foods?” We assessed the association between receiving advice and the following predictors: a diabetes diagnosis, 7 single risk factors for type 2 diabetes, and total number of risk factors. Results Among respondents without diabetes or risk factors for diabetes, 7.4% received low-fat dietary advice; 70.6% of respondents with diabetes received advice. Respondents with diabetes were almost twice as likely to receive advice as respondents without diabetes or its risk factors. As the number of risk factors increased, the likelihood of receiving low-fat dietary advice increased. Although unadjusted advice rates increased during the study period, the likelihood of receiving advice decreased. Conclusion Although most participants with diabetes received low-fat dietary advice, almost one-third did not. Low-fat dietary advice was more closely associated with the total number of diabetes risk factors than the presence of diabetes. Increasing rates of diabetes and diabetes risk factors are outpacing increases in provision of low-fat dietary advice.

Association of treatment modality for depression and burden of comorbid chronic illness in a nationally representative sample in the United States.

OBJECTIVE We examined associations between treatment modality for depression and morbidity burden. We hypothesized that patients with higher numbers of co-occurring chronic illness would be more likely to receive recommended treatment for depression with both antidepressant medication and psychotherapy. METHODS Using a retrospective cross-sectional design, we analyzed data on 165,826 people over 16 years from 2004 to 2008. Using a single multinomial logistic regression model, we examined the likelihood of treatment modality for depression: no treatment, psychotherapy alone, medication alone, and psychotherapy and medication. We examined the following predictors of therapy: (a) morbidity burden; (b) five specific chronic conditions individually: diabetes mellitus II, coronary artery disease, congestive heart failure, hypertension, and chronic obstructive pulmonary disease or asthma; and (c) sociodemographic factors. RESULTS The likelihood of any treatment for depression, specifically psychotherapy with medication, increased with the number of co-occurring illnesses. We did not find a clear pattern of association between the five specific conditions and treatment modality, although we identified treatment patterns associated with multiple sociodemographic factors. CONCLUSIONS This study provides insight into the relationship between multimorbidity and treatment modalities which could prove helpful in developing implementation strategies for the dissemination of evidence-based approaches to depression care.

Physician Acceptance of a Physician‐Pharmacist Collaborative Treatment Model for Hypertension Management in Primary Care

Physician‐pharmacist collaborative care (PPCC) is effective in improving blood pressure (BP) control, but primary care provider (PCP) engagement in such models has not been well‐studied. The authors analyzed data from PPCC referrals to 108 PCPs, for patients with uncontrolled hypertension, assessing the proportion of referral requests approved, disapproved, and not responded to, and reasons for disapproval. Of 2232 persons with uncontrolled hypertension, PPCC referral requests were sent for 1516 (67.9%): 950 (62.7%) were approved, 406 (26.8%) were disapproved, and 160 (10.6%) received no response. Approval rates differed widely by PCP with a median approval rate of 75% (interquartile range, 41%–100%). The most common reasons for disapproval were: PCP prefers to manage hypertension (19%), and BP controlled per PCP (18%); 8% of cases were considered too complex for PPCC. Provider acceptance of a PPCC hypertension clinic was generally high and sustained but varied widely among PCPs. No single reason for disapproval predominated.

Expanding the CONSORT Figure: Increasing Transparency in Reporting on External Validity

INTRODUCTION There are major problems with failure to replicate research findings. Contributing to this problem is a failure to report on factors related to external validity. Frequently, researchers have little knowledge whether findings apply more generally, especially to low-resource settings and underserved populations. The CONSORT flow diagram has improved reporting on variables related to internal validity, but it has very limited detail on issues related to external validity. A recent CONSORT update and other publications have called for more transparent reporting on external validity and context, and information regarding the sustainability of interventions. All of these elements influence the generalizability of findings from outcomes research. METHODS Drawing on theory, a prior meeting, and recent recommendations for reporting factors related to external validity, the authors propose an expansion of the basic CONSORT flow diagram for clinical trials to concisely summarize these data that recent CONSORT statements and other guidelines have recommended. RESULTS The authors propose the use of an expanded CONSORT figure and illustrate its utility with an example. The expanded CONSORT figure adds data about participation and representativeness at the levels of settings and staff, and about intervention sustainability after project support ends. The authors provide an expanded CONSORT figure reporting template, and demonstrate its use. CONCLUSIONS Improving transparent reporting on external validity by using the proposed expanded CONSORT figure would help to address both the scientific replication crisis and health equity concerns. This figure provides a method to efficiently address the representativeness, generalizability, and sustainability of outcomes research.