Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies

<i>Objective:</i> This study aims to: (1) identify the frequency of severe and level 2 hypoglycemia presenting in people with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting; (2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population. <p><i>Research Design and Methods:</i> A cross-sectional survey study in adults with type 1 diabetes using CGMs >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. </p> <p><i>Results: </i>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 (<i>P</i><0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (<i>P</i>=0.038).</p> <p><i>Conclusions:</i> Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in people with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may remain to impact the effectiveness of glucose self-management.</p>

Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies

<i>Objective:</i> This study aims to: (1) identify the frequency of severe and level 2 hypoglycemia presenting in people with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting; (2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population. <p><i>Research Design and Methods:</i> A cross-sectional survey study in adults with type 1 diabetes using CGMs >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. </p> <p><i>Results: </i>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 (<i>P</i><0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (<i>P</i>=0.038).</p> <p><i>Conclusions:</i> Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in people with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may remain to impact the effectiveness of glucose self-management.</p>

Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies

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.

Hypoglycemia with lactic acidosis caused by a new MRPS2 gene mutation in a Chinese girl: a case report

Background Mitochondrial ribosomal protein S2 (MRPS2) gene mutation, which is related to severe hypoglycemia and lactic acidosis, is rarely reported globally. Case presentation We report a case of a new MRPS2 gene mutation in a Chinese girl who presented with hypoglycemia and lactic acidosis. A homozygous C.412C > G variant that could cause complex oxidative phosphorylation deficiency and had not been reported before was identified. The clinical manifestations included recurrent vomiting, hypoglycemia, lactic acidosis, sensorineural hearing loss, and gall bladder calculi. Hypoglycemia and lactic acidosis improved after the administration of sugary liquid and supportive treatments. Conclusions Recurrent hypoglycemia with lactic acidosis and sensorineural hearing loss should lead to suspicion of mitochondrial defects and the early refinement of genetic tests.

Severe Hypoglycemia Increases Dementia Risk and Related Mortality: A Nationwide, Population-Based Cohort Study

Context There are few studies focused on the relationship between hypoglycemia and new-onset dementia in patients with type 2 diabetes and no study regarding mortality of dementia after hypoglycemia. Objective We investigated the effect of severe hypoglycemia on dementia subtypes and its relation to overall mortality in patients with type 2 diabetes. Methods We evaluated incident dementia, including Alzheimer disease and vascular dementia, among health checkup participants aged 40 years or older in the National Health Insurance System in Korea from January 2009 to December 2015. Episodes of severe hypoglycemia were examined for 3 years before the date of the health checkup. Results Among 2 032 689 participants (1 172 271 men, 860 418 women), 14 443 (0.7%) experienced severe hypoglycemia, during a mean follow-up period of 6.9 ± 1.7 years. Individuals in the severe hypoglycemia group were more likely to be diagnosed with dementia compared to individuals without severe hypoglycemia (23.3% vs 7.3%; P &lt; .001) and the overall incidence of Alzheimer disease was higher than vascular dementia. Dementia risk rose with increasing number of severe hypoglycemic episodes (1 episode [hazard ratio (HR) = 1.54; 95% CI, 1.48-1.60], 2 or more episodes [HR = 1.80; 95% CI, 1.66-1.94]). Overall mortality was higher in participants with dementia, but without severe hypoglycemia (HR = 2.03; 95% CI, 1.96-2.10) and severe hypoglycemia, but without dementia (HR = 4.24; 95% CI, 4.29-4.40), and risk of death was highest in those with both severe hypoglycemia and dementia (HR = 5.08; 95% CI, 4.83-5.35). Conclusion Severe hypoglycemia is associated with dementia, especially Alzheimer disease and mortality; together, they have an additive effect on overall mortality.

Association of low fasting C-peptide levels with cardiovascular risk, visit-to-visit glucose variation and severe hypoglycemia in the Veterans Affairs Diabetes Trial (VADT)

Aims Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia. Materials and methods Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants. Results There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range (< 0.50 nmol/l, HR 1.30 [95%CI 1.05–1.60], p = 0.02) and with rising levels in the high range (> 1.23 nmol/l, 1.27 [1.00–1.63], p = 0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60–0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate − 0.12 [SE 0.01]; ARV, − 0.10 [0.01]) (p < 0.0001 all). The association of low C-peptide levels with CVD risk was independent of cardiometabolic risk factors (1.48 [1.17–1.87, p = 0.001) and remained associated with CVD when tested in the same model with severe hypoglycemia and glucose CV. Conclusions Low C-peptide levels were associated with increased CVD risk in advanced type 2 diabetes. The association was independent of increases in glucose variation or severe hypoglycemia. C-peptide levels may predict future glucose control patterns and CVD risk, and identify phenotypes influencing clinical decision making in advanced type 2 diabetes.

Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes

Background and Purpose: Patients with type 2 diabetes (T2D) have increased risk of cardiovascular disease (CVD), encompassing myocardial infarction, stroke, and peripheral vascular disease. We hypothesized that those biomarkers indicative of acute ischemic stroke (AIS) seen in large vessel occlusion (LVO) may also be elevated in T2D and further enhanced by stress conditions; therefore, these proteins represent potentially predictive biomarkers for those T2D patients at high risk of AIS.Methods: We performed an exploratory proteomic analysis in control subjects (n = 23) versus those with type 2 diabetes (T2D) (n = 23) who underwent a hyperinsulinemic clamp study to transient severe hypoglycemia [blood glucose &lt;2.0 mmol/L (36 mg/dl)] in a prospective case-control study. We compared these proteins described as diagnostic and prognostic biomarkers for AIS due to LVO: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE1), thrombospondin-1 (THBS1), pro-platelet basic protein (PPBP), and cadherin 1 (CDH1).Results: At baseline (BL), PPBP (p &lt; 0.05), THBS1 (p &lt; 0.05), and CDH1 (p &lt; 0.01) were elevated in T2D; LYVE1 was not different between controls and T2D subjects at BL or at subsequent timepoints. PPBP and THBS1 tended to increase at hypoglycemia in both cohorts, though reached significance only in controls (p &lt; 0.05), returning to BL levels post-hypoglycemia. CDH1 levels were higher in T2D at BL, at hypoglycemia and up to 2-h posthypoglycemia, thereafter reverting to BL levels.Conclusion: Elevated levels of PPBP, THBS1, and CDH1, circulatory proteins suggested as biomarkers of AIS due to LVO, may, in T2D patients, be prognostically indicative of a cohort of T2D patients at increased risk of ischaemic stroke. Prospective studies are needed to determine if this reflects future clinical risk.Clinical trial reg. no: NCT03102801.