Objective: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in patients with type 1 diabetes (T1D) not using a continuous glucose monitoring (CGM) system. The current study investigated the prevalence of IAH and its relationship with severe hypoglycemia in T1D patients using CGM systems. Methods: This cross-sectional observational study enrolled 135 patients with T1D and ongoing real-time CGM use. A survey was conducted to assess hypoglycemia awareness with the Gold, Clarke, and Pedersen-Bjergaard questionnaires and the 6-month history of severe hypoglycemia. Other diabetes histories and the CGM glucose data were collected. Results: The Gold, Clarke, and Pedersen-Bjergaard questionnaires demonstrated the overall prevalence of IAH/abnormal awareness to be 33.3%, 43.7%, and 77.0%, respectively. Participant age and duration of T1D were consistently related to IAH or hypoglycemia unawareness with all three questionnaires (P<.05). Amongst the patients using CGM for >6 months, 24.5% were found to have at least one episode of severe hypoglycemia in the preceding 6 months. IAH identified by the Gold and Clarke questionnaires and hypoglycemia unawareness identified by the Pedersen-Bjergaard questionnaire were related to 6-, 4.63-, and 5.83-fold increased risk of severe hypoglycemia (P = .001, .004, and .013), respectively. IAH identified by the Gold/Clarke questionnaires was associated with a longer duration of CGM glucose <54 mg/dL and higher glucose coefficients of variation (P<.05). Conclusion: IAH is highly prevalent and related to a higher risk for severe hypoglycemia in T1D patients using CGM.

IAT after TP performed in our facility with an off-site islet isolation laboratory shows islet yield and rates of insulin independence that are comparable to other large centers with on-site laboratories.

Older adults are at risk of physical inactivity as they encounter debilitating life events. It is not known how insulin sensitivity is affected by modest short-term physical inactivity and recovery in healthy older adults, nor how insulin sensitivity is related to changes in serum and muscle ceramide content. Healthy older adults (aged 64-82 years, five females, seven males) were assessed before (PRE), after 2 weeks of reduced physical activity (RA) and following 2 weeks of recovery (REC). Insulin sensitivity (hyperinsulinaemic-euglyceamic clamp), lean mass, muscle function, skeletal muscle subfraction, fibre-specific, and serum ceramide content and indices of skeletal muscle inflammation were assessed. Insulin sensitivity decreased by 15 ± 6% at RA (driven by men) but rebounded above PRE by 14 ± 5% at REC. Mid-plantar flexor muscle area and leg strength decreased with RA, although only muscle size returned to baseline levels following REC. Body fat did not change and only minimal changes in muscle inflammation were noted across the intervention. Serum and intramuscular ceramides (nuclear/myofibrillar fraction) were modestly increased at RA and REC. However, ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults. Short-term inactivity induced insulin resistance in older adults in the absence of significant changes in body composition (i.e. fat mass) are not related to changes in ceramides.

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.

Context Little evidence exists regarding the positive and negative impacts of continuous glucose monitor system (CGM) alarm settings for diabetes control in patients with type 1 diabetes (T1D). Objective Evaluate the associations between CGM alarm settings and glucose outcomes. Design and Setting A cross-sectional observational study in a single academic institution. Patients and Main Outcome Measures CGM alarm settings and 2-week CGM glucose information were collected from 95 T1D patients with &gt; 3 months of CGM use and ≥ 86% active usage time. The associations between CGM alarm settings and glucose outcomes were analyzed. Results Higher glucose thresholds for hypoglycemia alarms (ie, ≥ 73 mg/dL vs &lt; 73 mg/dL) were related to 51% and 65% less time with glucose &lt; 70 and &lt; 54 mg/dL, respectively (P = 0.005; P = 0.016), higher average glucose levels (P = 0.002) and less time-in-range (P = 0.005), but not more hypoglycemia alarms. The optimal alarm threshold for &lt; 1% of time in hypoglycemia was 75 mg/dL. Lower glucose thresholds for hyperglycemia alarms (ie, ≤ 205 mg/dL vs &gt; 205 mg/dL) were related to lower average glucose levels and 42% and 61% less time with glucose &gt; 250 and &gt; 320 mg/dL (P = 0.020, P = 0.016, P = 0.007, respectively), without more hypoglycemia. Lower alarm thresholds were also associated with more alarms (P &lt; 0.0001). The optimal alarm threshold for &lt; 5% of time in hyperglycemia and hemoglobin A1c ≤ 7% was 170 mg/dL. Conclusions Different CGM glucose thresholds for hypo/hyperglycemia alarms are associated with various hypo/hyperglycemic outcomes. Configurations to the hypo/hyperglycemia alarm thresholds could be considered as an intervention to achieve therapeutic goals.

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OBJECTIVE This study aimed to 1) identify the frequency of severe and level 2 hypoglycemia presenting in individuals with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting, and; 2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population. RESEARCH DESIGN AND METHODS A cross-sectional survey study in adults with type 1 diabetes using CGMs &gt;6 months was conducted at a large tertiary academic center. Participant demographics, 6-month severe hypoglycemia history, hypoglycemia beliefs (with the Attitude to Awareness of Hypoglycemia questionnaire), and 4-week CGM glucose data were collected. Statistical analysis was performed to assess the presentation of severe and level 2 hypoglycemia and identify associated risk factors. RESULTS A total of 289 participants were recruited (including 257 participants with CGM data within the last 3 months). Of these, 25.6% experienced at least one severe hypoglycemic episode in the last 6 months, and 13.6% presented with ≥1% of time in level 2 hypoglycemia on CGMs. Reporting beliefs about prioritizing hyperglycemia avoidance was associated with severe hypoglycemia development (P &lt; 0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (P = 0.038). CONCLUSIONS Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in individuals with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may continue to impact the effectiveness of glucose self-management.

Background Mechanisms underlying physical inactivity‐induced insulin resistance are not well understood. In addition to a role in muscle repair, immune cell populations such as macrophages may regulate insulin sensitivity. Aim The aim of this study was to examine if the dynamic changes in insulin sensitivity during and after recovery from reduced physical activity corresponded to changes in skeletal muscle macrophages. Methods In this prospective clinical study, we collected muscle biopsies from healthy older adults (70 ± 2 years, n = 12) before and during a hyperinsulinaemic‐euglycaemic clamp and this occurred before (PRE) and after 2‐week reduced physical activity (RA), and following 2‐week of recovery (REC). Insulin sensitivity (hyperinsulinaemic‐euglycaemic clamp), skeletal muscle mRNA expression of inflammatory markers, and immunofluorescent quantification of skeletal muscle macrophages, myofibre‐specific satellite cell and capillary content were assessed. Results Insulin sensitivity was decreased following reduced activity and rebounded following recovery above PRE levels. We observed an increase (P < 0.01) in muscle macrophages (CD68+CD206+: 190 [55, 324]; CD11b+CD206+: 117 [28, 205]% change from PRE) and CD68 (2.4 [1.4, 3.4]‐fold) and CCL2 (1.9 [1.3, 2.5]‐fold) mRNA following RA concurrent with increased (P < 0.03) satellite cells (55 [6, 104]%) in slow‐twitch myofibres. Moreover, the distance of satellite cells to the nearest capillary was increased 7.7 (1.7, 13.7) µm in fast‐twitch myofibres at RA (P = 0.007). Changes in macrophages were positively associated with increased insulin sensitivity following RA (R > 0.57, P < 0.05). Conclusion These findings suggested that a dynamic response of skeletal muscle macrophages following acute changes in physical activity in healthy older adults is related to insulin sensitivity.