Diabetes Mellitus Participants Research Articles

Neuropathic pain is not associated with serum vitamin D but is associated with female gender in patients with type 2 diabetes mellitus

ObjectiveNeuropathic pain is a common complication of diabetes mellitus (DM). Patients may complain of several neuropathic symptoms including impaired peripheral sensation, numbness, tingling, burning, and pain. Because these symptoms may...

Effect of tele-rehabilitation on glucose control, exercise capacity, physical fitness, muscle strength and psychosocial status in patients with type 2 diabetes: A double blind randomized controlled trial

AimTo determine the effect of a tele-rehabilitation (TR) program on glucose control, exercise capacity, physical fitness, muscle strength and psychosocial status in patients with type 2 diabetes mellitus (DM). MethodFifty type 2 DM participants were enrolled in the study and divided randomly into two groups; TR (n = 25, mean age: 52.82 ± 11.86) or control (n = 25, mean age: 53.04 ± 10.45) group. Participants in the TR group performed breathing and callisthenic exercises, three times a week, for 6 weeks, at home by internet based video conferences. Outcome measures including, HbA1c level, 6 min walk testing, physical fitness and muscle strength dynamometer measurement, Beck Depression Inventory were performed before and after the 6 weeks. ResultsHbA1c (p = 0.00), 6 min walking distance (p = 0.00), physical fitness subparameters; sit-up (p = 0.00), sit-and-reach (p = 0.04), back scratch (p = 0.00), lateral flexion right (p = 0.04), left (p = 0.00) and time up go tests (p = 0.00), muscles strength (p = 0.00); deltoideus-anterior, middle, quadriceps femoris and gluteus maximus, and depression levels (p = 0.00) changed significantly (p = 0.00) in TR groups. There were no significant improvements in control group (p > 0.05). ConclusionOur findings suggest that TR interventions found to be safe and effective, and may be an alternative treatment model for type 2 DM management. In addition to these health benefits, patients and rehabilitation team may save time, labor and treatment costs by using TR.

Elevated Fasting Blood Glucose Level Increases the Risk of Cognitive Decline Among Older Adults with Diabetes Mellitus: The Shanghai Aging Study

Several studies have demonstrated that the elevated fasting blood glucose (FBG) may increase the risk of incident dementia in older adults with or without diabetes mellitus (DM). However, similar results are rarely reported in Chinese population. This study aimed to demonstrate the association between FBG and risk of incident cognitive decline in older Chinese adults. We prospectively followed up 1,555 dementia-free participants with baseline FBG measurement in the Shanghai Aging Study. We identified 126 incident dementia cases across a mean of 5.2 years. Cumulative dementia incidence in type II DM participants with higher FBG (>6.1 mmol/L) increased most dramatically, second with that of non-DM participants with higher FBG, than that of participants with lower FBG (≤6.1 mmol/L). DM participants had a significant higher risk of incident dementia (adjusted HR 1.51, 95% CI 1.25-1.82) by every 1 mmol/L increment of FBG. Among DM participants, baseline FBG was positively related to the rate of annual decline of MMSE (β= 0.10, p = 0.0018). Our results suggest that especially in people with type II DM, effective blood glucose control may help to prevent cognitive impairment in later life.

Leisure time physical activity is associated with better metabolic control in adults with type 1 and type 2 diabetes mellitus: A cross-sectional study from two public hospitals in Chile

AimTo examine the association between leisure time physical activity (LTPA) and metabolic control, in adults with diabetes mellitus (DM). MethodsA cross-sectional study was conducted in two hospitals (Santiago, Chile) with 101 type 1 (mean 34.4±12.3 years) and 100 type 2 DM (mean 57.8±5.2 years) adults. Glycated hemoglobin level (A1C) was obtained, and LTPA levels were estimated through the Global Physical Activity Questionnaire.Multiple linear regression models were fitted evaluating the independent effect of LTPA, sociodemographic, cardiovascular risk factors and other types of physical activity (PA) on metabolic control. ResultsDM participants which reported no LTPA had higher levels of A1C (type 1 mean A1C: 8.8±1.5% and type 2 mean A1C: 9.2±1.4%) compared to those who fulfilled PA recommendations of ≥150min/week (type 1 mean A1C: 8.0±1.6% and type 2 mean A1C: 8.1±1.4%).Regression analysis showed that A1C levels were negatively associated with ≥150min/week on LTPA in type 1 (b=−0.25; 95%CI −0.16 to −0.01) and type 2 DM (b=−0.24; 95%CI −0.29 to −0.02) participants. ConclusionLeisure time physical activity may be considered as an efficient and inexpensive non-pharmacological tool for DM treatment. Hence, healthcare professionals should educate and promote PA since primary-care diagnosis in addition to prevent disease-related complications.

Abdominal circumference profiles of macrosomic infants born to mothers with or without hyperglycemia in China

Objectives: Serial measurements of sonographic fetal abdominal circumference (AC) are useful for monitoring fetal growth during pregnancy and are essential for predicting macrosomia. The study was aiming to compare the AC profiles of infants born to mothers with or without hyperglycemia in Chinese population.Subjects and methods: The “GDM Prevalence Study (GPS)” was a large study conducted in 22 hospitals in three large cities in China, which included 34,085 NGT (normal glucose tolerant) women, 8272 GDM (gestational diabetes mellitus) women and 729 DM (diabetes mellitus) women. A total of 116,740 scans and 103,377 valid AC measurements were performed for the NGT, GDM and DM groups at different gestational age. AC profiles and fetal growth rates at different stages of pregnancy were compared between different groups.Results: The overall AC growth rate (β) was higher in the macrosomia group than in the no macrosomia group in NGT (β =10.250 versus 9.541, p < .001), GDM (β = 10.572 versus 9.705, p < .001) and DM (β = 11.363 versus 9.924, p < .001) pregnancies. Significant differences were observed between NGT-macrosomia, GDM-macrosomia and DM-macrosomia. Significant differences were also noted between NGT-no macrosomia, GDM-no macrosomia and DM-no macrosomia women. Participants in NGT-macrosomia group exhibited larger AC values than NGT-no macrosomia group beginning at 21 gestational weeks, and GDM-macrosomia group exhibited larger AC values than GDM-no macrosomia group beginning at 22 gestational weeks. AC growth rate was higher in NGT-macrosomia and GDM-macrosomia groups than in the corresponding no macrosomia groups between 22 and 30 gestational weeks.Conclusions: The overall AC growth rates are higher in macrosomia group compared to the no macrosomia group in NGT, GDM as well as DM participants. The significant difference of AC growth rates in NGT-macrosomia and GDM-macrosomia indicate the possible differential underlying mechanisms in developing macrosomia with or without hyperglycemia exposure. Our study demonstrate that larger fetal AC measurements around 21–22 weeks are associated with subsequent diagnosis of macrosomia, suggesting that macrosomia management should be initiated much earlier than we thought.

Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients

To compare the rates of visual field (VF) loss and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients with or without type 2 diabetes mellitus (DM). Cohort study. A total of 197 eyes (55 eyes of 32 POAG patients with DM in POAG/DM group and 142 eyes of 111 age-matched POAG patients without DM in POAG/DM- group) were included from the Diagnostic Innovations in Glaucoma Study (DIGS). Type 2 DM participants were defined by self-report of DM history and use of antidiabetic medication. The rates of VF loss and RNFL loss were compared in POAG eyes with and without DM using univariate and multivariable mixed-effects models. The median (interquartile range) follow-up was 5.7 years (4.0, 6.4). The mean rate of global RNFL loss in the POAG/DM group was 2-fold slower than in the POAG/DM- group overall (-0.40μm/year vs-0.83μm/year, respectively P= .01). Although a slower rate of VF mean deviation and pattern standard deviation loss was found in the POAG/DM group compared to the POAG/DM- group, the difference was not statistically significant. POAG patients with treated type 2 DM, who had no detectable diabetic retinopathy, had significantly slower rates of RNFL thinning compared to those without diagnosed DM.

Differences in pain thresholds elicited by intraoral electrical stimuli between individuals with and without diabetes mellitus.

There is little evidence of sensation in individuals with diabetes mellitus (DM) in the dental research field. We investigated whether pain thresholds (PTs) differ between individuals with and without DM (non-DM; NDM). To this end, we assessed whether PTs obtained from the oral cavity, hands, and feet differed from each other and across groups, and whether PTs differed for the three current frequencies used for testing (2000Hz, 250Hz, and 5Hz). Pain threshold measurements were obtained from the oral mucosa and the tips of the fingers and toes of 56 volunteers, including 21 individuals with DM (12 men and 9 women, average age: 72.1±4.7years) and 35 NDM individuals (17 males and 18 females, average age: 51.2±23.9years) using the Neurometer CPT/C® device to deliver electrical stimulation. A single operator obtained PT measurements from around the left greater palatine foramen and from the tip of the left first finger and of the left great toe. Individuals with DM had significantly lower PT values than those without DM. The PT values for the oral cavity, hands, and feet differed significantly from each other (foot>hand, foot>oral cavity, hand>oral cavity). Moreover, there was a significant difference in the PT values for 5Hz and 2000Hz, as well as for 250Hz and 2000Hz. This study concluded that PT values derived from DM participants are lower than those from NDM participants, although PT measurements varied across regions and with current frequency.

Heart failure and inflammation-related biomarkers as predictors of new-onset diabetes in the general population.

There is a strong reciprocal relationship between heart failure (HF) and diabetes mellitus (DM). Shared pathophysiological mechanisms might be a possible explanation. Therefore, we hypothesised that biomarkers linked to HF would also predict new-onset type 2 DM in the general population. We utilized the Prevention of Vascular and Renal End-stage Disease (PREVEND) cohort (mean age 48.9years, 51% female) to study the relationship between HF and DM in 7953 participants free of baseline HF and DM. Multiple HF-related, inflammation-related and renal function-related biomarkers were evaluated regarding their predictive utility in new-onset DM. Incidence of DM in participants who developed HF was 11.8%, versus 5.4% in those who had not developed HF (p<0.001). Incidence of HF in participants who developed DM was 8.5%, versus 3.8% in those who had not developed DM (p<0.001). Classical HF biomarkers, NT-proBNP and hs-TnT were not associated with an increased risk for new-onset DM. However, inflammatory biomarkers hs-CRP [hazard ratio (HR) 1.16, (95% CI 1.05 to 1.29), p=0.005], procalcitonin [HR 1.34, (95% CI 1.07 to 1.69), p=0.012] and PAI-1 [HR 1.55, (95% CI 1.37 to 1.75), p<0.001] remained significantly associated with new-onset DM, even after multivariable adjustment for established predictors of DM. Although HF and DM have a strong correlation with each other, systemic biomarkers that predict HF do not have a predictive value in new-onset DM. This suggests that other, indirect, pathophysiological mechanisms related to inflammation may explain their strong relation.

Diabetes mellitus and the risk of bladder cancer: A PRISMA-compliant meta-analysis of cohort studies.

Epidemiologic studies have reported inconsistent results regarding the relationship between diabetes mellitus (DM) and the incidence of bladder cancer. This comprehensive systematic review and meta-analysis explored and evaluated this relationship in participants with different characteristics. Studies indexed in the PubMed, Embase, and the Cochrane Library databases that compared bladder cancer incidence mortality between DM and non-DM participants were included in the present study. The relative risks (RRs) of a random-effects model were used to assess these associations. The final analysis included 21 cohort studies, involving a total of 13,505,643 participants. Overall, DM was associated with an increased risk of bladder cancer or cancer mortality when compared with non-DM participants (RR: 1.23; 95% confidence interval [CI]: 1.12-1.35; P < .001). Furthermore, DM had a harmful impact on subsequent bladder cancer risk in men compared with those without DM (RR: 1.23; 95% CI: 1.06-1.42; P = .005), whereas no significant relationship was observed between DM and bladder cancer in women (RR: 1.24; 95% CI: 0.95-1.61; P = .119). There was no significant gender difference for this relationship (ratio of RR: 0.99; 95% CI: 0.73-1.34; P = .958). In addition, cancer incidence (RR: 1.21; 95% CI: 1.09-1.35; P < .001) and cancer mortality (RR: 1.25; 1.17-1.35; P < .001) both increased in DM patients. Finally, smoking status and follow-up duration might also affect this relationship in men and women. The findings of this study indicated that DM was associated with elevated bladder cancer or cancer mortality risk, especially in men. This relationship in women requires further exploration.

At-Risk Driving Behavior in Drivers with Diabetes: A Neuroergonomics Approach

This pilot study tackles the overarching need for driver-state detection through real-world measurements of driver behavior and physiology in at-risk drivers with type 1 diabetes mellitus (DM). 35 drivers (19 DM, 14 comparison) participated. Real-time glucose levels were measured over four weeks with continuous glucose monitor (CGM) wearable sensors. Contemporaneous real-world driving performance and behavior were measured with in-vehicle video and electronic sensor instrumentation packages. Results showed clear links between at-risk glucose levels (particularly hypoglycemia) and changes in driver performance and behavior. DM participants often drove during at-risk glucose levels (low and high) and showed cognitive impairments in key domains for driving, which are likely linked to frequent hypoglycemia. The finding of increased driving risk in DM participants was mirrored in state records of crashes and traffic citations. Combining sensor data and phenotypes of driver behavior can inform patients, caregivers, safety interventions, policy, and design of supportive in-vehicle technology that is responsive to driver state.

The Associations among Insulin Resistance, Hyperglycemia, Physical Performance, Diabetes Mellitus, and Cognitive Function in Relatively Healthy Older Adults with Subtle Cognitive Dysfunction.

Insulin resistance (IR), diabetes mellitus (DM), sarcopenia, and cognitive dysfunction are thought to be mutually associated. We conducted a comprehensive assessment of the relationships among IR, gait speed, hyperglycemia, and DM by cross-sectionally analyzing the baseline data of an interventional study for cognitive preservation with physical exercise (the TOyota Preventional Intervention for Cognitive decline and Sarcopenia [TOPICS]). The participants (n = 444) were relatively healthy older individuals who had mild cognitive impairment without dementia, and 61 of the participants had DM. Slow gait speed and hyperglycemia were associated with cognitive dysfunction, mainly in the executive function domain, whereas IR was associated with memory impairment. The participants with DM had lower general cognition and executive function. Executive dysfunction in the DM participants seemed to be partly explained by hyperglycemia and/or slow gait speed. Our findings confirmed that IR, DM, sarcopenia, and cognitive dysfunction are mutually associated in complex ways. Understanding the mechanisms underlying these associations will lead to effective strategies to prevent and treat cognitive dysfunction in older individuals.

OP.1D.04] SUBCLINICAL LEFT VENTRICULAR DIASTOLIC DYSFUNCTION AND INCIDENT TYPE 2 DIABETES MELLITUS

Objective: Subclinical left ventricular (LV) diastolic dysfunction in diabetes mellitus (DM) is a common finding and represent an early sign of diabetic cardiomyopathy. Yet, the relations of LV diastolic dysfunction and incidence of type 2 DM remain undefined. Design and method: We followed up 1817 non-diabetic participants (mean age, 54 years; 48% men) free of cardiovascular disease from the Korean Genome and Epidemiology Study biennially for 6 years. LV structure and function were measured by tissue Doppler imaging echocardiography. Subclinical LV diastolic dysfunction was defined using E/Em ratio, and left atrial volume index, and age-specific cutoff limit for early diastolic (Em) velocity. Results: During 6-year follow-up, 273 participants (15%) developed type 2 DM. In a multivariate-adjusted regression model, lower Em velocity (odd ratio [OR], 0.858; 95% confidence interval [CI], 0.771 – 0.955; P = 0.005), higher E/Em ratio (OR, 1.076; 95% CI, 1.014 – 1.143, P = 0.016), and the presence of LV diastolic function (OR, 1.794; 95% CI, 1.286 – 2.504, P = 0.001) were associated with the development of type 2 DM in prediabetes. However, no echocardiographic parameters were independent predictors of incident type 2 DM in participants with normal glucose tolerance. Conclusions: In a community-based cohort undergoing 6 years of follow-up, progression to type 2 DM in prediabetic participants could be predicted by the presence of subclinical LV diastolic dysfunction. This association is independent of age, prevalence of overweight, obesity, and hypertension, and initial fasting blood glucose.

Impaired fasting glucose is associated with increased severity of subclinical coronary artery disease compared to patients with diabetes and normal fasting glucose: evaluation by coronary computed tomographic angiography

ObjectiveThis study was designed to evaluate the severity of subclinical atherosclerosis in patients with asymptomatic impaired fasting glucose (IFG) compared to those with diabetes mellitus (DM) and normal fasting glucose...

Effect of Vitamin D supplementation on glycemic control in Type 2 diabetes subjects in Lagos, Nigeria.

Introduction:Improvement of glycemic control reduces the risk of diabetic complications. Reports suggest that Vitamin D supplementation improves glycemia. However, there are no data on the influence of Vitamin D on diabetes mellitus (DM) in Nigeria.Objective:To determine the effect of Vitamin D supplementation on glycemic control in Type 2 DM (T2DM) participants with Vitamin D deficiency.Design:This was a single-blind, prospective randomized placebo-controlled trial, involving T2DM participants attending the Diabetes Clinic of the Lagos University Teaching Hospital. Forty-two T2DM participants with poor glycemic control and Vitamin D deficiency were selected following a prior cross-sectional study on 114 T2DM participants for the determination of Vitamin D status and glycemia. These participants were randomized into two equal groups of treatment and placebo arms.Intervention:Three thousand IU of Vitamin D3 were given to the participants in the treatment arm. Glycemic status was determined at baseline and after 12 weeks. Statistical analysis was performed using Statistical Package for Social Sciences version 20. P < 0.05 was considered statistically significant.Results:Vitamin D3 supplementation resulted in a significant improvement in serum Vitamin D level and fasting plasma glucose in the treatment arm compared to placebo. There was a nonsignificant reduction in the mean HbA1c level in the treatment group after 12 weeks of Vitamin D3 supplementation (Z = −1.139; P = 0.127) compared to the placebo group, which had a further increase in the mean HbA1c level (Z = −1.424; P = 0.08). The proportion of participants with poor glycemic control (HbA1c > 6.5%) who converted to good control after Vitamin D supplementation was significantly higher in the treatment arm compared to placebo (P < 0.05).Conclusion:Vitamin D3 supplementation in persons with T2DM and Vitamin D deficiency results in a significant improvement in glycemic control.

Correlates Between Colorectal Cancer Screening and Diabetes Mellitus Among Residents of Ohio Appalachia

Introduction: Colorectal cancer (CRC) is the third mostly commonly diagnosed cancer and leading cause of cancer mortality in the United States. Notably, Appalachian regions have higher CRC incidence and mortality rates and lower screening rates than non-Appalachian regions. Previous investigation has shown that having a primary care provider, patient-provider communication, and social influence are correlated with CRC screening patterns among Appalachian Ohio residents. However, it is not established whether these factors differ among residents with diabetes mellitus (DM), an independent risk factor of CRC, as compared to those without. Aim: To characterize CRC screening behaviors and barriers among patients with and without DM. Methods: We conducted interviews with and examined medical record data from Appalachian Ohio residents 50-75 years of age from September 2009 to September 2013. We identified correlates of being within CRC screening guidelines using multivariable logistic regression. Multiple imputation using the fully conditional specification method was used to impute both income and the CRC screening outcome where missing. In order to determine whether there were demographic factors that differentially predicted CRC screening in DM vs. non-DM participants, we fit multivariable logistic regression models that included an interaction between the factor and DM for each of the imputed datasets. Demographic predictors were considered separately. Estimates were combined using SAS PROC MIANALYZE (v9.3, SAS Institute, Cary, NC). Results: There were 4,401 participants included in the analysis. Among the 3,771 participants whose CRC screening status was known, 590 (15.6%) had DM and 1,359 (36.0%) were within CRC screening guidelines. Using the multiple imputations, participants with DM who asked their doctor to order a screening test (OR=5.05, 95% CI: 2.47-10.34) had higher odds of screening than those without DM (OR=2.43, 95% CI: 1.92-3.07, interaction p=0.04). Similarly, divorced, widowed or separated participants with DM had higher odds of CRC screening compared to never married participants (OR=1.98, 95% CI: 1.17-3.37) than those without DM (OR=1.20, 95% CI: 0.76- 1.89, interaction p=0.02). However, overall, there was no significant difference in the CRC screening rate between patients with DM and those without (OR=0.94, 95% CI: 0.79-1.09). Conclusion: Adherence to CRC screening guidelines is low among Appalachian Ohio residents. Although the association between DM and CRC risk is well-established, there was no significant difference in the screening rate among residents with DM as compared to those without DM. However, this study underscores the importance of targeting patient-provider communication in strategies to improve CRC screening rates.

Diabetes Mellitus is Associated With Low Secretion Rates of Immunoglobulin A in Saliva.

BackgroundThe association between diabetes mellitus (DM) and low secretory immunoglobulin A (s-IgA) secretion rates is one mechanism suspected of influencing susceptibility to infections among DM patients. However, several studies have shown contradictory results. We examined these two factors to seek evidence of an association among older people.MethodsWe analyzed a prospective cohort of 2306 subjects (1209 men and 1097 women) around 64 years old from the New Integrated Suburban Seniority Investigation (NISSIN) Project in Nisshin, Japan. DM statuses were ascertained from levels of fasting plasma glucose and HbA1c, and s-IgA secretion rates were obtained from 5-min saliva samples. We used an analysis of covariance adjusted for possible confounders to compare s-IgA secretion rates according to DM status.Resultss-IgA secretion rates in DM participants were lower than in those classified as normal (18.6 µg/min vs 15.0 µg/min, P = 0.03), even after elimination of the effects of possible confounders.ConclusionsDM was associated with lower s-IgA secretion rates. This suggests that lower s-IgA levels may be a mechanism of susceptibility to infection in individuals with DM.

Is Helicobacter pylori infection associated with glycemic control in diabetics?

To investigate whether Helicobacter pylori (H. pylori) infection is associated with glycemic control and whether hyperglycemia is modified by eradication therapy. The databases of PubMed, Cochrane Library, Chinese BioMedicine Web Base and Chinese Science and Technology Journals were searched from inception to June 2014. Studies examining the association between H. pylori infection and glycemic control and/or the effect of eradication treatment on glycemic control in diabetic humans were eligible for inclusion. Meta-analyses were conducted using the Review Manager software version 5.2. The outcome measures are presented as weighed mean differences (WMDs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed by the Cochran Q test and the I(2) statistic. A total of 21 relevant publications were identified. A meta-analysis of 11 studies with 513 patients with diabetes mellitus (DM) showed significantly lower glycosylated hemoglobin (HbA1c) levels in the H. pylori-negative than H. pylori-positive DM participants (WMD = 0.43, 95%CI: 0.07-0.79; P = 0.02). In children and adolescents with type 1 DM (T1DM), there was a positive association between H. pylori infection and HbA1c level (WMD = 0.35, 95%CI: 0.05-0.64; P = 0.02), but there was no difference in those with type 2 DM (T2DM, WMD = 0.51, 95%CI: -0.63-1.65; P = 0.38). A meta-analysis of six studies with 325 T2DM participants showed a significant difference in the fasting plasma glucose levels between H. pylori-positive and H. pylori-negative participants (WMD = 1.20, 95%CI: 0.17-2.23; P = 0.02). Eradication of H. pylori did not improve glycemic control in the T2DM participants in a three-month follow-up period (HbA1c decrease: WMD = -0.03, 95%CI = -0.14-0.08; P = 0.57; fasting plasma glucose decrease: WMD = -0.06, 95%CI: -0.36-0.23; P = 0.68). Glycemic control was significantly better in T1DM participants who were not reinfected than in those who were reinfected (HbA1c: WMD = 0.72, 95%CI: 0.32-1.13: P = 0.00). H. pylori infection is associated with poorer glycemic control in T1DM patients, but eradication may not improve glycemic control in DM in a short-term follow-up period.

Effect of Type 2 Diabetes Mellitus on Epicardial Adipose Tissue Volume and Coronary Vasomotor Function

Patients with coronary artery disease and/or type 2 diabetes mellitus (DM) generally exhibit more epicardial adipose tissue (EAT) than healthy controls. Recently, it has been proposed that EAT affects vascular function and structure by secreting proinflammatory and vasoactive substances, thereby potentially contributing to the development of cardiovascular disease. In the present study, the interrelation of EAT, coronary vasomotor function, and coronary artery calcium was investigated in patients with and without DM, who were evaluated for coronary artery disease. Myocardial blood flow (MBF) was assessed at rest and during adenosine-induced hyperemia using [(15)O]-water positron emission tomography combined with computed tomography to quantify coronary artery calcium and EAT in 199 patients (46 with DM). In this cohort (mean age 58 ± 10 years), the patients with DM had a greater body mass index, heart rate, and systolic blood pressure at rest (all p <0.05). Coronary artery calcium and the EAT volumes were comparable between those with and without DM. Both patient groups showed comparable MBF at rest and coronary vascular resistance. A lower hyperemic MBF and coronary flow reserve (CFR) and greater hyperemic coronary vascular resistance (all p <0.05) was observed in the patients with DM. A pooled analysis showed a positive association of EAT volume with hyperemic coronary vascular resistance but not with the MBF at rest, hyperemic MBF, or coronary vascular resistance at rest. In the group analysis, the EAT volume was inversely associated with hyperemic MBF (r = -0.16, p = 0.05) and CFR (r = -0.17, p = 0.04) and positively with hyperemic coronary vascular resistance (r = 0.26, p = 0.002) only in patients without DM. Multivariate regression analysis, adjusted for age, gender, and body mass index, showed an independent association between the EAT volume and hyperemic MBF (β = -0.16, p = 0.02), CFR (β = -0.16, p = 0.04), and hyperemic coronary vascular resistance (β = 0.25, p <0.001) in the non-DM group. In conclusion, these results suggest a role for EAT in myocardial microvascular dysfunction; however, once DM has developed, other factors might be more dominant in contributing to impaired myocardial microvascular dysfunction.

Exercise Stress Tests for Detecting Myocardial Ischemia in Asymptomatic Patients With Diabetes Mellitus

The predominant cause of death in diabetes mellitus (DM) is coronary artery disease (CAD). Little is known about prevalence of silent ischemia in developing nations. We compared prevalence of silent ischemia in DM to a control group by exercise myocardial perfusion imaging (MPI) and electrocardiogram (ECG) in developing nations. The prospective multinational Ischemia Assessment with Exercise imaging in Asymptomatic Diabetes study recruited participants at 12 sites in Asia, Africa, and Latin America. DM participants were age- and gender-matched 2:1 to non-DM individuals with ≥1 CAD risk factor. Subjects underwent exercise tests that were interpreted in core labs in blinded fashion. The study included 392 DM and 205 control participants. Among participants with diagnostic ECGs, a similar proportion of DM and controls had ischemic ECG (15% vs 12%, p = 0.5). A significantly higher proportion of DM group had MPI abnormalities compared with controls (26% vs 14%, p <0.001). In participants with ischemia on MPI, only 17% had ischemic ECG, whereas in those without ischemia on MPI, 10% had ischemic ECG. In a multivariable model, DM was independently associated with abnormal MPI (odds ratio 2.1, 95% confidence interval 1.3-3.5, p = 0.004). Women were less likely to have ischemia by MPI than men (10% vs 30%, p <0.001) and concordance between ECG and MPI was much worse in women. In conclusion, in this large prospective study, asymptomatic DM participants had (1) more ischemia by exercise MPI than ECG, (2) more ischemia by MPI but not ECG than control group, and (3) ischemia by MPI was less in women than men.

Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus

Studies of experimental diabetes mellitus (DM) suggest that increased nitric oxide (NO) bioactivity contributes to renal hyperfiltration. However, the role of NO in mediating hyperfiltration has not been fully elucidated in humans. Our aim was to examine the effect of NO synthase inhibition on renal and peripheral vascular function in normotensive subjects with uncomplicated type 1 DM. Renal function and brachial artery flow-mediated vasodilatation (FMD) were measured before and after an intravenous infusion of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NMMA) in 21 healthy control and 37 type 1 DM patients. Measurements in DM participants were made under clamped euglycemic conditions. The effect of l-NMMA on circulating and urinary NO metabolites (NO(x)) and cGMP and on urinary prostanoids was also determined. Baseline characteristics were similar in the two groups. For analysis, the DM patients were divided into those with hyperfiltration (DM-H, n = 18) and normal glomerular filtration rate (GFR) levels (DM-N, n = 19). Baseline urine NO(x) and cGMP were highest in DM-H. l-NMMA led to a decline in GFR in DM-H (152 ± 16 to 140 ± 11 ml·min(-1)·1.73 m(-2)) but not DM-N or healthy control participants. The decline in effective renal plasma flow in response to l-NMMA (806 ± 112 to 539 ± 80 ml·min(-1)·1.73 m(-2)) in DM-H was also exaggerated compared with the other groups (repeated measures ANOVA, P < 0.05), along with declines in urinary NO(x) metabolites and cGMP. Baseline FMD was lowest in DM-H compared with the other groups and did not change in response to l-NMMA. l-NMMA reduced FMD and plasma markers of NO bioactivity in the healthy control and DM-N groups. In patients with uncomplicated type 1 DM, renal hyperfiltration is associated with increased NO bioactivity in the kidney and reduced NO bioactivity in the systemic circulation, suggesting a paradoxical state of high renal and low systemic vascular NO bioactivity.