Vitamin D Insufficiency is Associated With Reduced Parasympathetic Nerve Fiber Function in Type 2 Diabetes

ObjectiveVitamin D insufficiency is prevalent in subjects with type 2 diabetes mellitus (T2DM) and is associated with peripheral neuropathy. However, there are little data regarding vitamin D status in patients with cardiovascular autonomic neuropathy. Our objective was to evaluate the association of cardiovascular autonomic function, 25-hydroxyvitamin D (25[OH]D) insufficiency (i.e., levels < 30 ng/mL), and multiple metabolic parameters in subjects with T2DM.MethodsWe examined 50 individuals with T2DM. Cardiovascular autonomic function (i.e., parasympathetic function) was assessed by RR-variation during deep breathing (i.e., mean circular resultant [MCR] and expiration/inspiration [E/I] ratio). Metabolic parameters included measures of adiposity, glycemic control, insulin resistance, calcium metabolism, and 25(OH)D.ResultsParticipants with 25(OH)D insufficiency (n = 26) were younger (66 ± 9 vs. 60 ± 10 years, P < .05), more insulin resistant, had a higher body mass index (BMI) and lower adiponectin levels. The MCR (39.5 ± 26.3 vs. 27.6 ± 17.2, P < .01) and E/I ratio (1.21 ± 0.17 vs. 1.15 ± 0.09, P < .01) were lower for those with 25(OH)D insufficiency after controlling for age. A stepwise selection procedure regressing MCR and E/I ratio on a number of metabolic parameters resulted in a model identifying age and 25(OH)D insufficiency as significant determinants for both measures. The interaction of age × 25(OH)D insufficiency was also included (MCR model, R² = 0.491, P < .001; E/I ratio, R² = 0.455, P < .001). Neither glycemic control nor other metabolic parameters were selected.ConclusionOur results suggest that 25(OH)D insufficiency is associated with reduced parasympathetic function, with a stronger association in younger persons with T2DM. Studies are needed to determine if vitamin D supplementation into the sufficient range could prevent or delay the onset of cardiovascular autonomic dysfunction. (Endocr Pract. 2015;21:174-181)     

Adiposity Predicts Cognitive Decline in Older Persons with Diabetes: A 2-Year Follow-Up

Background

The mechanisms related to cognitive impairment in older persons with Type 2 diabetes (DM) remains unclear. We tested if adiposity parameters and body fat distribution could predict cognitive decline in older persons with DM vs. normal glucose tolerance (NGT).

Methodology

693 older persons with no dementia were enrolled: 253 with DM in good metabolic control; 440 with NGT (age range:65–85 years). Longitudinal study comparing DM and NGT individuals according to the association of baseline adiposity parameters (body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC) and total body fat mass) to cognitive change (Mini Mental State Examination (MMSE), a composite score of executive and attention functioning (CCS) over time.

Findings

At baseline, in DM participants, MMSE correlated with WHR (β = −0.240; p = 0.043), WC (β = −0.264; p = 0.041) while CCS correlated with WHR (β = −0.238; p = 0.041), WC (β = −0.326; p = 0.013) after adjusting for confounders. In NGT subjects, no significant correlations were found among any adiposity parameters and MMSE, while CCS was associated with WHR (β = −0.194; p = 0.036) and WC (β = −0.210; p = 0.024). Participants with DM in the 3^rd tertile of total fat mass showed the greatest decline in cognitive performance compared to those in 1^st tertile (tests for trend: MMSE(p = 0.007), CCS(p = 0.003)). Logistic regression models showed that 3^rd vs. 1^st tertile of total fat mass, WHR, and WC predicted an almost two-fold decline in cognitive function in DM subjects at 2^nd yr (OR 1.68, 95%IC 1.08–3.52).

Conclusions

Total fat mass and central adiposity predict an increased risk for cognitive decline in older person with DM.     

Upstroke Time Per Cardiac Cycle is Associated with Cardiovascular Prognosis in Type 2 Diabetes

Objective: Upstroke time per cardiac cycle (UTCC) in the lower extremities has been found to be predictive of cardiovascular mortality in the general population. Therefore, the purpose of the study was to test the associations between increasing UTCC and outcomes in patients with type 2 diabetes.Methods: A total of 452 patients with type 2 diabetes (age, 67.5 ± 8.6 years; male, 54%) registered in a share-care program participated in the study at an outpatient clinic in Taipei Veterans General Hospital across a mean of 5.8 years. Primary outcomes were all-cause mortality hospitalization for coronary artery disease, stroke, revascularization, amputation, and diabetic foot syndrome. Secondary end-point outcome was all-cause mortality.Results: Increment of UTCC associations with primary and secondary outcomes were undertaken prior to baseline characteristic adjustments. A UTCC of 20.1% exhibited the greatest area under curve (AUC), sensitivity, and specificity balance to predict composite events in receiver operating curves (AUC, 0.63 &lsqb;P = .001]; sensitivity, 67.7%; specificity, 54.9%). Sixty-four composite events and 17 deaths were identified from medical records. UTCC ≥20.1% was associated with the occurrence of composite events and an increased risk of mortality. For composite events, an adjusted hazard ratio (HR) of 2.45 and 95% confidence interval (CI) of 1.38 to 4.35 (P = .002) were calculated. For all-cause mortality, an adjusted HR of 1.91 and 95% CI of 0.33 to 10.99 (P = .467) were calculated.Conclusion: Increasing UTCC was associated with cardiovascular outcomes in patients with type 2 diabetes. Therefore, UTCC is advocated as a noninvasive screening tool for ambulatory patients with type 2 diabetes.Abbreviations: CAD = coronary artery disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; HR = hazard ratio; PAD = peripheral artery disease; UTCC = upstroke time per cardiac cycle     

Cognitive Training Improves Sleep Quality and Cognitive Function among Older Adults with Insomnia

Study Objectives

To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia.

Design

Participants (n = 51) were randomly allocated to a cognitive training group (n = 34) or to an active control group (n = 17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants'' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated.

Setting

Community setting: residential sleep/performance testing facility.

Participants

Fifty-one older adults with insomnia (aged 65–85).

Interventions

Eight weeks of computerized cognitive training for older adults with insomnia.

Results

Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep.

Conclusions

New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00901641","term_id":"NCT00901641"}}NCT00901641http://clinicaltrials.gov/ct2/show/NCT00901641     

Two Urinary Peptides Associated Closely With Type 2 Diabetes Mellitus

Objective

To monitor of type 2 diabetes more simply, conveniently and noninvasively, we are trying to identify the potential urinary peptides that associated with different stages of glucose control in type 2 diabetes mellitus.

Methods

Firstly, we collected urine samples from type 2 diabetic patients and normal controls. These type 2 diabetic patients were divided into two groups according to fasting plasma glucose (FPG) and hemoglobin A1c% (HbA1c), respectively. Magnetic beads based weak cation exchange chromatography (MB-WCX) was used to condense urinary peptides. The eluates were then analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Subsequently, ClinProt was used to profile and screen the polypeptide patterns based on different methods of grouping in diabetic patients and normal controls. Finally, the amino acid sequences of differentially expressed peptides were identified by nano-liquid chromatography-tandem mass spectrometry and the protein sources of the corresponding peptide were matched in IPI Human database.

Results

Proteomics analysis found two up-regulated peptide (m/z 2756.1 and m/z 3223.2) representations in diabetic subjects, and the two peptides increased with increases in the amount of glycosylated hemoglobin. Further, the parallelism between m/z 3223.2 and glycosylated hemoglobin was better than the parallelism between m/z 2756.1 and glycosylated hemoglobin. Area under the receiver operating characteristic of the two peptides was 0.722 and 0.661, respectively. The above-mentioned peptide m/z 2756.1 was further identified as fragment of fibrinogen alpha chain precursor and m/z 3223.2 was fragment of prothrombin precursor.

Conclusion

These results suggested the two urinary biomarkers enable monitor of type 2 diabetes patients with different stages of glucose control.     

Nordic Walking Improves Cardiometabolic Parameters,Fitness Performance,and Quality of Life in Older Adults With Type 2 Diabetes

ObjectiveTo assess the effect of Nordic walking (NW) on cardiometabolic health, physical performance, and well-being in sedentary older adults with type 2 diabetes (T2D).MethodsFifteen subjects with T2D (female, 5; male, 10; age, 65 ± 6.2 years [mean ± standard deviation]; body mass index, 27.3 ± 4.9 kg/m² [mean ± standard deviation]) were enrolled in a 6-month NW training program. The fasting glucose and glycosylated hemoglobin levels, lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), systolic blood pressure (SBP), and diastolic blood pressures were measured before and after the intervention. Participants’ quality of life (Short-Form Health Survey) and physical fitness (6-minute walking test) were also evaluated.ResultsCompared with baseline, NW significantly improved the fasting glucose level (103.5 ± 18.5 vs 168.7 ± 37.7 mg/dL, P = .01), SBP (121.8 ± 12.2 vs 133 ± 14.4 mm Hg, P = .02), physical fitness (759.88 ± 69 vs 615.5 ± 62.6 m, P < .001), and both mental health (54.5 ± 4.4 vs 45.7 ± 5.6, P < .01) and physical health (49.8 ± 4.7 vs 40.3 ± 5.9, P < .01). The levels of glycosylated hemoglobin (6.15% ± 0.8% vs 6.4% ± 1%, P = .46), total cholesterol (162.2 ± 31.2 vs 175.5 ± 28.8 mg/dL, P = .13), low-density lipoprotein cholesterol (95.2 ± 24.2 vs 106.3 ± 32.3 mg/dL, P = .43), and triglycerides (135.5 ± 60.8 vs 127.6 ± 57.4 mg/dL, P = 0.26) improved without reaching significance.ConclusionNW training improved the glycemic levels, SBP, physical fitness, and perception of quality of life in older adults with T2D. NW represents a suitable complementary strategy to improve the global health status in this population.     

Factors Associated with Weight Control in Older Adults

Dieting behaviors in a sample of 183 overweight older adults were studied to assess how they were influenced by six cognitive, behavioral, emotional, and social variables. Membership in a weight control program was also evaluated to assess whether it affected these relationships. Responses indicated that reports of high quality dieting behaviors were associated with higher levels of depression and less effective coping skills. Dieting behaviors among subjects who were participants in weight loss programs were not as strongly associated with less effective coping skills, but were associated with external health locus-of-control. The degree of social support had a limited impact on dieting behaviors, while measures of optimism and health status were unrelated to dieting behaviors. We concluded that older adults, especially those who diet independently, are likely to experience significant stress associated with weight loss efforts. Weight loss programs for older adults might produce better outcomes if they focus on reducing depression and stress associated with dieting.     

Predicting Cognitive Function from Clinical Measures of Physical Function and Health Status in Older Adults

Introduction

Current research suggests that the neuropathology of dementia—including brain changes leading to memory impairment and cognitive decline—is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies.

Methods

We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1–L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation.

Results

Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year.

Discussion

We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a clinical setting.     

Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults

Background

Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control.

Methods and Findings

The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03). Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group to C. coccoides-E. rectale group correlated positively and significantly with plasma glucose concentration (P = 0.04) but not with BMIs. Similarly, class Betaproteobacteria was highly enriched in diabetic compared to non-diabetic persons (P = 0.02) and positively correlated with plasma glucose (P = 0.04).

Conclusions

The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.     

Biopsychosocial Factors and Cognitive Function in Cat Ownership and Attachment in Community-dwelling Older Adults

ABSTRACT

Few studies consider the health benefits of pet ownership from a biopsychosocial perspective, and a paucity of studies investigate cat ownership. The current study was designed to determine if psychosocial factors (stress, loneliness, and depression), biological levels of stress and inflammation (salivary cortisol, interleukin-1β, and C-reactive protein [CRP]), and cognitive function were associated with companion cat ownership/attachment in community-dwelling older adults. Community-dwelling older adults (n = 96, mean age = 76.6 years) who either owned a cat and no dog (n = 41) or owned neither a cat nor a dog (n = 55) completed questionnaires (Perceived Stress Scale, Revised–UCLA Loneliness Scale, Geriatric Depression Scale-Short Form, Montreal Cognitive Assessment, and Lexington Attachment to Pets Scale) and provided saliva specimens which were assayed for stress and inflammatory biomarkers. The majority of participants screened positive for mild cognitive impairment, reported low levels of stress, loneliness, and depression, and the biomarkers reflected fairly low levels of stress and inflammation. Binary logistic regression analysis revealed that psychosocial factors, salivary biomarkers, and cognitive function were not significantly associated with cat ownership. Age was the only significant predictor of cat ownership (OR = 0.92, p < 0.01) with the odds of cat ownership decreasing by 8.3% per year of advancing age. On average, cat owners were “somewhat attached” to their cats; however, 26% were “strongly attached” to their cats. Correlation analyses revealed the level of attachment to cats was not associated with study outcomes. These results show that cat ownership declined with each advancing year, which lessens the opportunity for older adults to form attachment bonds. The level of pet attachment supports the consideration of cats as a source of an attachment relationship for older adults, including those with cognitive impairment.     

Multi-Scale Glycemic Variability: A Link to Gray Matter Atrophy and Cognitive Decline in Type 2 Diabetes

Objective

Type 2 diabetes mellitus (DM) accelerates brain aging and cognitive decline. Complex interactions between hyperglycemia, glycemic variability and brain aging remain unresolved. This study investigated the relationship between glycemic variability at multiple time scales, brain volumes and cognition in type 2 DM.

Research Design and Methods

Forty-three older adults with and 26 without type 2 DM completed 72-hour continuous glucose monitoring, cognitive tests and anatomical MRI. We described a new analysis of continuous glucose monitoring, termed Multi-Scale glycemic variability (Multi-Scale GV), to examine glycemic variability at multiple time scales. Specifically, Ensemble Empirical Mode Decomposition was used to identify five unique ultradian glycemic variability cycles (GVC_1–5) that modulate serum glucose with periods ranging from 0.5–12 hrs.

Results

Type 2 DM subjects demonstrated greater variability in GVC_3–5 (period 2.0–12 hrs) than controls (P<0.0001), during the day as well as during the night. Multi-Scale GV was related to conventional markers of glycemic variability (e.g. standard deviation and mean glycemic excursions), but demonstrated greater sensitivity and specificity to conventional markers, and was associated with worse long-term glycemic control (e.g. fasting glucose and HbA1c). Across all subjects, those with greater glycemic variability within higher frequency cycles (GVC_1–3; 0.5–2.0 hrs) had less gray matter within the limbic system and temporo-parietal lobes (e.g. cingulum, insular, hippocampus), and exhibited worse cognitive performance. Specifically within those with type 2 DM, greater glycemic variability in GVC_2–3 was associated with worse learning and memory scores. Greater variability in GVC₅ was associated with longer DM duration and more depression. These relationships were independent of HbA1c and hypoglycemic episodes.

Conclusions

Type 2 DM is associated with dysregulation of glycemic variability over multiple scales of time. These time-scale-dependent glycemic fluctuations might contribute to brain atrophy and cognitive outcomes within this vulnerable population.     

Hypoglycemia Requiring Ambulance Services in Patients with Type 2 Diabetes is Associated with Increased Long-Term Mortality

ObjectiveTo report population burden of hypoglycemia requiring ambulance services and long term outcomes thereafter, among people with type 2 diabetes (T2D).MethodsWe retrieved all ambulance calls made by T2D for hypoglycemia in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2009.ResultsSeven hundred eighteen calls were made by 503 T2D (age 69 ± 12 years, 51% male), of which 328 (65%) were on insulin (INS), 54 (11%) on insulin + noninsulin agents (NIAI), 95 (19%) on sulphonylurea alone or in combination with other noninsulin agents (SFU), 21 (4%) on nonsulphonylurea noninsulin agents (NSFU), and 5 (1%) on no therapy (excluded from further analysis). NSFU had lower repeated calls (INS 25%, NIAI 26%, SFU 12%, NSFU 5%; P = .02), emergency room transportation (ERT) (INS 62%, NIAI 67%, SFU 68%, NSFU 38%; P = .06), and hospitalizations (INS 31%, NIAI 46%, SFU 38%, NSFU 19%; P = .02) compared to other groups. In multivariable mortality model, increased age (P<.001) was associated with an increased risk of death, whereas hypoglycemia predisposing comorbidities (chronic liver disease, end stage renal disease, adrenal insufficiency) (P = .06) were associated with a borderline increased risk, but no association was found with treatment group, repeated calls, ERT, hospitalization and baseline diabetic end organ complications.ConclusionTo our knowledge, we report the first estimate of hypoglycemia requiring ambulance services among T2D, in contemporary clinical practice. NSFU cohort was associated with lower repeated calls, ERT, and hospitalizations compared to other therapeutic programs. Predictors of mortality post-hypoglycemia were age and hypoglycemia predisposing comorbidities. (Endocr Pract. 2013;19:29-35)     

Factors Associated With the Time to Next Attack in Neuromyelitis Optica: Accelerated Failure Time Models With Random Effects

Background and Objective

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system with a relapsing and remitting course. We aimed to identify factors associated with the time to next attack, including the effect of the natural disease course and the diverse treatment regimens, by applying a longitudinal statistical analysis to the individual attacks of each patient.

Methods

In total, 184 acute attacks among 58 patients with either NMO or NMO spectrum disorder with anti-aquaporin-4 antibody were assessed retrospectively. Patient demographics, clinical characteristics at each attack, and type of treatment during inter-attack periods were assessed. The dependent variable was defined as the time from each attack to the next attack (inter-attack interval). An exponential accelerated failure time model with shared gamma frailty was adapted for statistical analysis.

Results

A multivariable analysis revealed that the time from each attack to the next attack in NMO increased independently by 1.31 times (95% confidence interval (CI), 1.02–1.67; p = 0.035) with each additional cumulative attack experienced, by 5.34 times (95% CI, 1.57–18.13; p = 0.007) with combined azathioprine treatment and continued oral prednisolone, and by 4.26 times (95% CI, 1.09–16.61; p = 0.037) with rituximab treatment.

Conclusion

The time to next attack in NMO can increase naturally in the later stages of the disease as the number of cumulative attacks increases. Nevertheless, both combined azathioprine treatment with continued oral prednisolone and rituximab treatment were also associated with a longer time to next attack, independently of the natural disease course of NMO.     

Neighbourhood Walkability and Daily Steps in Adults with Type 2 Diabetes

Introduction

There is evidence that greater neighbourhood walkability (i.e., neighbourhoods with more amenities and well-connected streets) is associated with higher levels of total walking in Europe and in Asia, but it remains unclear if this association holds in the Canadian context and in chronic disease populations. We examined the relationships of different walkability measures to biosensor-assessed total walking (i.e., steps/day) in adults with type 2 diabetes living in Montreal (QC, Canada).

Materials and Methods

Participants (60.5±10.4 years; 48.1% women) were recruited through McGill University-affiliated clinics (June 2006 to May 2008). Steps/day were assessed once per season for one year with pedometers. Neighbourhood walkability was evaluated through participant reports, in-field audits, Geographic Information Systems (GIS)-derived measures, and the Walk Score^®. Relationships between walkability and daily steps were estimated using Bayesian longitudinal hierarchical linear regression models (n = 131).

Results

Participants who reported living in the most compared to the least walkable neighbourhoods completed 1345 more steps/day (95% Credible Interval: 718, 1976; Quartiles 4 versus 1). Those living in the most compared to the least walkable neighbourhoods (based on GIS-derived walkability) completed 606 more steps per day (95% CrI: 8, 1203). No statistically significant associations with steps were observed for audit-assessed walkability or the Walk Score^®.

Conclusions

Adults with type 2 diabetes who perceived their neighbourhoods as more walkable accumulated more daily steps. This suggests that knowledge of local neighborhood features that enhance walking is a meaningful predictor of higher levels of walking and an important component of neighbourhood walkability.     

Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

Background

Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).

Methodology and Principal Findings

Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).

Conclusion

Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.     

Mortality Associated with Diabetes and Cardiovascular Disease in Older Women

Background

Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aimed to assess whether diabetes was associated with a similar risk of total and cause-specific mortality as a history of CVD in older women.

Methodology/Principal Findings

We studied 9218 women aged 68 years or older enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up period of 11.7 years and compared all-cause, cardiovascular and coronary heart disease mortality among 4 groups: non-diabetic women with and without existing CVD, diabetic women with and without existing CVD. Mean (SD) age of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8% reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The multivariate adjusted risk of cardiovascular mortality was increased among both non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97–2.74, P<0.001) and diabetic women without CVD (HR 2.06, CI: 1.62–2.64, P<0.001) compared to non-diabetic women without existing CVD. All-cause, cardiovascular and coronary mortality of non-diabetic women with CVD were not significantly different from diabetic women without CVD.

Conclusions/Significance

Older diabetic women without CVD have a similar risk of cardiovascular mortality compared to non-diabetic women with pre-existing CVD. The equivalence of diabetes and CVD seems to extend to older women, supporting current guidelines for cardiovascular prevention.     

Disruptions in Brain Networks of Older Fallers Are Associated with Subsequent Cognitive Decline: A 12-Month Prospective Exploratory Study

Cognitive impairment and impaired mobility are major public health concerns. There is growing recognition that impaired mobility is an early biomarker of cognitive impairment and dementia. The neural basis for this association is currently unclear. We propose disrupted functional connectivity as a potential mechanism. In this 12-month prospective exploratory study, we compared functional connectivity of four brain networks– the default mode network (DMN), fronto-executive network (FEN), fronto-parietal network (FPN), and the primary motor sensory network (SMN) – between community-dwelling older adults with ≥ two falls in the last 12 months and their non-falling counterparts (≤ one fall in the last 12 months). Functional connectivity was examined both at rest and during a simple motor tapping task. Compared with non-fallers, fallers showed more connectivity between the DMN and FPN during right finger tapping (p = 0.04), and significantly less functional connectivity between the SMN and FPN during rest (p≤0.05). Less connectivity between the SMN and FPN during rest was significantly associated with greater decline in both cognitive function and mobility over the12-month period (r = −0.32 and 0.33 respectively; p≤0.04). Thus, a recent history of multiple falls among older adults without a diagnosis of dementia may indicate sub-clinical changes in brain function and increased risk for subsequent decline.     

Efficacy and Safety of Ideglira in Older Patients with Type 2 Diabetes

Objective: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years.Methods: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1–receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V).Results: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, -1.0% &lsqb;-1.5; -0.6]_{95% confidence interval &lsqb;CI]}, -0.8% &lsqb;-1.0; -0.5]_{95% CI}, and -0.9% &lsqb;-1.3; -0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 &lsqb;0.2; 1.6]_{95% CI} &lsqb;P = .242]; 0.3 &lsqb;0.1; 0.5]_{95% CI} &lsqb;P<.001], and 11.8 &lsqb;3.3; 42.8]_{95% CI} &lsqb;P<.001] for DUAL II, V, and III, respectively).Conclusion: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall.Abbreviations: A1C = hemoglobin A1C; AE = adverse event; CI = confidence interval; Degludec = insulin degludec; EOT = end of trial; ETD = estimated treatment difference; FPG = fasting plasma glucose; GLP-1RA = glucagon-like peptide 1 receptor agonist; IDegLira = insulin degludec/liraglutide; IGlar U100 = insulin glargine 100 U/mL; SU = sulfonylurea; T2D = type 2 diabetes     

Understanding the Relationship between Type 2 Diabetes Mellitus and Falls in Older Adults: A Prospective Cohort Study

Background

Older adults with type 2 Diabetes Mellitus are at increased risk of falling. The current study aims to identify risk factors that mediate the relationship between diabetes and falls.

Methods

199 older adults (104 with diabetes and 95 healthy controls) underwent a medical screening. Gait (GAITRite®), balance (AccuGait® force plate), grip strength (Jamar®), and cognitive status (Mini-Mental State Examination and Clock Drawing Test) were assessed. Falls were prospectively recorded during a 12-month follow-up period using monthly calendars.

Results

Compared to controls, diabetes participants scored worse on all physical and cognitive measures. Sixty-four participants (42 diabetes vs. 22 controls) reported at least one injurious fall or two non-injurious falls (“fallers”). Univariate logistic regression identified diabetes as a risk factor for future falls (Odds Ratio 2.25, 95%CI 1.21–4.15, p = 0.010). Stepwise multiple regressions defined diabetes and poor balance as independent risk factors for falling. Taking more medications, slower walking speed, shorter stride length and poor cognitive performance were mediators that reduced the Odds Ratio of the relationship between diabetes and faller status relationship the most followed by reduced grip strength and increased stride length variability.

Conclusions

Diabetes is a major risk factor for falling, even after controlling for poor balance. Taking more medications, poorer walking performance and reduced cognitive functioning were mediators of the relationship between diabetes and falls. Tailored preventive programs including systematic medication reviews, specific balance exercises and cognitive training might be beneficial in reducing fall risk in older adults suffering from diabetes.     

Menstrual and Reproductive Function in Women With Type 1 Diabetes

Objective: Menstrual irregularities, reproductive abnormalities, and androgen excess are reported to be more prevalent in women with type 1 diabetes (T1D). The objective of this study was to investigate the prevalence of menstrual irregularities, reproductive abnormalities, and androgen excess among women with T1D and their age-matched controls.Methods: A survey requesting information regarding menstrual and reproductive histories was administered to all participants. Results were stratified according to age (18 to 40, 40 to 50, and >50 years).Results: There were no significant differences between women with and without diabetes in age at menarche, cycle length, or androgen excess in any group. Women who self-reported difficulty with glycemic control were more likely to report irregular menses than controls (P = .04). Among women who reported ever being pregnant, there were fewer pregnancies (P = .02) and live births (P = .002) in women with T1D. Women with T1D reported a lower frequency of oral contraceptive use (P = .003), despite being less likely to smoke (P = .016).Conclusion: Menstrual and reproductive abnormalities were not observed more frequently in women with T1D in this study. Subtle but measurable differences in menstrual and reproductive function were confined to the subgroup of women who perceived poor control of their diabetes. Additional prospective studies of T1D and menstrual and reproductive function would be useful.Abbreviations: BMI = body mass index CVD = cardiovascular disease DCCT = Diabetes Control and Complications Trial FAD = Familial Autoimmune and Diabetes HbA_1c = glycated hemoglobin HC = hormonal contraception T1D = type 1 diabetes