Impaired awareness of hypoglycemia (IAH) is a reduction in the ability to recognize low blood glucose levels that would otherwise prompt an appropriate corrective therapy. Identified in approximately ...25% of patients with type 1 diabetes, IAH has complex pathophysiology, and might lead to serious and potentially lethal consequences in patients with diabetes, particularly in those with more advanced disease and comorbidities. Continuous glucose monitoring systems can provide real‐time glucose information and generate timely alerts on rapidly falling or low blood glucose levels. Given their improvements in accuracy, affordability and integration with insulin pump technology, continuous glucose monitoring systems are emerging as critical tools to help prevent serious hypoglycemia and mitigate its consequences in patients with diabetes. This review discusses the current knowledge on IAH and effective diagnostic methods, the relationship between hypoglycemia and cardiovascular autonomic neuropathy, a practical approach to evaluating cardiovascular autonomic neuropathy for clinicians, and recent evidence from clinical trials assessing the effects of the use of CGM technologies in patients with type 1 diabetes with IAH.
Hypoglycemia can induce hypoglycemia unawareness, which puts patients at higher risk for developing severe hypoglycemia. Hypoglycemia and its relationship with cardiovascular autonomic neuropathy are complex and remain to be further elucidated. Continuous glucose monitoring systems (CGMs) can help reduce hypoglycemia for those with hypoglycemia unawareness.
Objective
To determine the associations between individual metabolic syndrome (MetS) components and peripheral neuropathy in a large population‐based cohort from Pinggu, China.
Methods
A ...cross‐sectional, randomly selected, population‐based survey of participants from Pinggu, China was performed. Metabolic phenotyping and neuropathy outcomes were performed by trained personnel. Glycemic status was defined according to the American Diabetes Association criteria, and the MetS using modified consensus criteria (body mass index instead of waist circumference). The primary peripheral neuropathy outcome was the Michigan Neuropathy Screening Instrument (MNSI) examination. Secondary outcomes were the MNSI questionnaire and monofilament testing. Multivariable models were used to assess for associations between individual MetS components and peripheral neuropathy. Tree‐based methods were used to construct a classifier for peripheral neuropathy using demographics and MetS components.
Results
The mean (SD) age of the 4002 participants was 51.6 (11.8) and 51.0% were male; 37.2% of the population had normoglycemia, 44.0% prediabetes, and 18.9% diabetes. The prevalence of peripheral neuropathy increased with worsening glycemic status (3.25% in normoglycemia, 6.29% in prediabetes, and 15.12% in diabetes, P < 0.0001). Diabetes (odds ratio OR 2.60, 95% CI 1.77–3.80) and weight (OR 1.09, 95% CI 1.02–1.18) were significantly associated with peripheral neuropathy. Age, diabetes, and weight were the primary splitters in the classification tree for peripheral neuropathy.
Interpretation
Similar to previous studies, diabetes and obesity are the main metabolic drivers of peripheral neuropathy. The consistency of these results reinforces the urgent need for effective interventions that target these metabolic factors to prevent and/or treat peripheral neuropathy.
Aim
To estimate the incidence of falls in individuals with type 2 diabetes compared to healthy controls and to describe the characteristics of fallers with type 2 diabetes in relation to motor ...dysfunction, postural instability and diabetic polyneuropathy (DPN).
Methods
This is a cross‐sectional study of individuals with type 2 diabetes with DPN (n = 54), without DPN (n = 38) and healthy controls (n = 39). Falls were recorded within the preceding year. DPN was defined by clinical scores and nerve conduction studies. Motor function was assessed by a 6‐min walk test (6 MWT), five‐time sit‐to‐stand test (FTSST) and isokinetic dynamometry at the non‐dominant ankle and knee. An instability index (ST) was measured using static posturography. Univariate and bivariate descriptive statistics were used for group comparisons.
Results
Compared with healthy controls, individuals with diabetes had a higher incidence of falls 36%, (n = 33) versus 15%, (n = 6), p = 0.02. There were no differences in falls when comparing individuals with and without DPN. Fallers had an impaired 6 MWT versus non‐fallers (450 ± 153 m vs. 523 ± 97 m respectively), a slower FTSST (11.9 ± 4.2 s vs. 10.3 ± 2.9 s respectively) and a higher ST (53 ± 29 vs. 41 ± 17 respectively), p < 0.02 for all.
Conclusion
Individuals with type 2 diabetes reported a higher number of falls within the preceding year compared to healthy controls, irrespective of the presence of DPN. The main factors associated with falls were increased postural instability, lower walking capacity and slower sit‐to‐stand movements. The 6 MWT, FTSST and posturography should be considered in future screening programs in identification of individuals at risk for falls.
Aim
To estimate the prevalence of sexual dysfunction in women with type 1 diabetes (T1D) compared with women without diabetes and to analyse associations between sexual dysfunction and the presence ...of chronic physical diabetes complications, diabetes distress and depression in women with T1D.
Methods
This cross‐sectional study was conducted in Norway, and 171 women with T1D and 60 controls completed the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). Diabetes distress was assessed with the Problem Areas in Diabetes (PAID) scale. Data on diabetes complications were retrieved from medical records. We performed logistic regression to estimate differences in the prevalence of sexual dysfunction (defined as FSFI ≤26.55) between women with T1D and women without diabetes and to examine associations of sexual dysfunction with chronic diabetes complications, diabetes distress and depression in women with T1D.
Results
The prevalence of sexual dysfunction was higher in women with T1D (50.3%) compared with the controls (35.0%; unadjusted odds ratio OR 1.89 95% confidence interval (CI) 1.06–3.37; adjusted OR 1.93 1.05–3.56). In women with T1D, sexual dysfunction was associated with both diabetes distress (adjusted OR 1.03 1.01–1.05) and depression (adjusted OR 1.28 1.12–1.46), but there were no clear associations with chronic diabetes complications (adjusted OR 1.46 0.67–3.19).
Conclusions
This study suggests that sexual dysfunction is more prevalent in women with T1D compared with women without diabetes. The study findings emphasize the importance of including sexual health in relation to diabetes distress and psychological aspects in diabetes care and future research.
Objective
To determine the burden and identify correlates of female sexual dysfunction (FSD) among women with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program ...(DPP) Outcomes Study (DPPOS).
Methods
The DPPOS visit included the Female Sexual Function Index (FSFI) to determine sexual function. Of 1464 participants, 1320 (90%) completed the (FSFI) and 426 were sexually active. A backward selection multivariable logistic regression model estimated the odds of FSD for sociodemographic, clinical, and diabetes‐related covariates.
Results
One hundred and eighty‐five (43%) had a score of ≤26.55 and met the criteria for FSD. After adjustment for DPP treatment and age, urinary incontinence (UI) (odds ratio OR = 1.91, 95% confidence interval CI = 1.15–3.17) and hysterectomy (OR = 1.89, 95% CI = 1.01–3.53) were associated with increased odds of FSD. Increased body mass index was protective for FSD (OR = 0.93 per kg/m2, 95% CI = 0.89–0.96). Michigan Neuropathy Screening Instrument‐based peripheral neuropathy (mean±SD scores 1.1±1.3 vs. 0.9±1.1, p < 0.0001) and Electrocardiogram (ECG)‐based autonomic dysfunction measures (mean ± SD heart rate levels 64.3 ± 6.8 vs. 65.6 ± 10.2, p = 0.008) were associated with FSD. There were no differences in diabetes rates between women who did (66.5%) and did not (66%) have (p = 0.7).
Conclusions
FSD is prevalent in women with PreD and T2D. Our findings suggest that FSD is associated with neuropathic complications commonly observed in PreD and T2D.
Objective
To estimate the prevalence of and risk factors for cardiovascular autonomic neuropathy (CAN) in adolescents and young adults with type 1 and type 2 diabetes enrolled in the SEARCH for ...Diabetes in Youth Study.
Methods
The study included 1646 subjects with type 1 diabetes (age 18 ± 4 years, diabetes duration 8 ± 2 years, HbA1c 9.1 ± 1.9%, 76% non‐Hispanic Whites) and 252 with type 2 diabetes (age 22 ± 4 years, diabetes duration 8 ± 2 years, HbA1c 9.2 ± 3.0%, 45% non‐Hispanic Blacks). Cross‐sectional and longitudinal risk factors were assessed at baseline and follow‐up visits. Area under the curve (AUC) was used to assess the longitudinal glycemic exposure and cardiovascular risk factors. CAN was assessed by time and frequency domain indices of heart rate variability (HRV). CAN was defined as the presence of ≥3 of 5 abnormal HRV indices.
Results
The prevalence of CAN was 12% in adolescents and young adults with type 1 diabetes and 17% in those with type 2 diabetes. Poor long‐term glycemic control (AUC HbA1c), high blood pressure, and elevated triglyceride levels were correlates of CAN in subjects with type 1 diabetes. In those with type 2 diabetes, CAN was associated with elevated triglycerides and increased urinary albumin excretion.
Conclusions
The prevalence of CAN in this multiethnic cohort of adolescents and young adults with type 1 and type 2 diabetes are comparable to those reported in adults with diabetes. Suboptimal glycemic control and elevated triglycerides were the modifiable risk factors associated with CAN.
Objective
This study explored the association of BMI and insulin sensitivity with cognitive performance in type 2 diabetes.
Methods
A cross‐sectional analysis of data from the baseline assessment of ...the Glycemia Reduction Approaches in Diabetes: a Comparative Effectiveness Study (GRADE) was conducted. BMI was used as a surrogate of adiposity and the Matsuda index as the measure of insulin sensitivity. Cognitive tests included the Spanish English Verbal Learning Test, the Digit Symbol Substitution Test, and the letter and animal fluency tests.
Results
Cognitive assessments were completed by 5018 (99.4%) of 5047 participants aged 56.7 ± 10.0 years, of whom 36.4% were female. Higher BMI and lower insulin sensitivity were related to better performance on memory and verbal fluency tests. In models including BMI and insulin sensitivity simultaneously, only higher BMI was related to better cognitive performance.
Conclusions
In this study, higher BMI and lower insulin sensitivity in type 2 diabetes were cross‐sectionally associated with better cognitive performance. However, only higher BMI was related to cognitive performance when both BMI and insulin sensitivity were considered simultaneously. The causality and mechanisms for this association need to be determined in future studies.
Aims/Introduction
Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, ...but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN.
Materials and Methods
Standardized CARTs (R‐R response to paced breathing, Valsalva, postural changes) and digitized 12‐lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted R‐R intervals (SDNN) and the root mean square of successive differences between normal‐to‐normal R‐R intervals (rMSSD) were measured from ECG. Sensitivity, specificity, probability of correct classification and Kappa statistics evaluated the agreement between ECG‐derived CAN and CARTs‐defined CAN.
Results
Participants with CARTs‐defined CAN had significantly lower SDNN and rMSSD compared with those without CAN (P < 0.001). The optimal cut‐off points of ECG‐derived CAN were <17.13 and <24.94 ms for SDNN and rMSSD, respectively. SDNN plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistic for SDNN was 0.41 (95% confidence interval 0.30–0.51) for the optimal cut‐off point, showing fair agreement with CARTs‐defined CAN. Combining SDNN and rMSSD optimal cut‐off points does not provide additional predictive power for CAN.
Conclusions
These analyses are the first to show the agreement between indices of heart rate variability derived from ECGs and the gold standard CARTs, thus supporting potential use as a measure of CAN in clinical research and clinical care.
Participants with cardiovascular reflex tests‐defined cardiovascular autonomic neuropathy (CAN) had significantly lower standard deviation of normally conducted R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals compared to those without CAN (P < 0.001). standard deviation of normally conducted R‐R intervals plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistics for standard deviation of normally conducted R‐R intervals was 0.41 (95% confidence interval 0.30–0.51) for the optimal cut‐off point, showing fair agreement with cardiovascular reflex tests‐defined CAN.
Aims
To test whether a long‐acting GLP‐1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function ...would affect the response. In addition, we sought to determine whether the drug would affect beta cell function.
Methods
We performed a randomized placebo‐controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C‐peptide. Seventy‐nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C‐peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug.
Results
At week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval CI 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C‐peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased.
Conclusion
Treatment with exenatide ER may have short‐term benefits in some individuals with T1D who are overweight or who have detectable levels of C‐peptide, but short‐term improvements were not sustained.
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