Search

Introduction: Hypoglycemia may be related to malnutrition or treatment of diabetes. An association between treatment with medical food and lower incidence of hypoglycemia among patients with diabetes and hypoalbuminemia has recently been shown., Aims: To study the association between hypoglycemia incidence and medical and nutrition treatment for diabetes., Methods: In this observational study, data was collected from electronic medical records. Included were patients with type 2 diabetes, admitted to internal medicine "E" at the Edith Wolfson Medical Center between 1.6.2016-31.5.2017. Logistic regression was implemented to assess the association between treatment for diabetes and hypoglycemia. Linear regression models were built to examine the association between treatment for diabetes and the number of hypoglycemic events., Results: Included were 221 patients (62.4% females, mean age 77.4 ± 12.0 years), 52 of them (23.5%) had hypoglycemia. The proportion of patients on medical food was 69.5±37.1%. According to logistic regression model, age (OR 1.034, CI 1.002-1.068, p=0.038), male sex (OR 2.941, CI 1.454-5.945, p=0.003) and treatment with insulin (OR 3.778, CI 1.831-7.794, p<0.001) were associated with hypoglycemia, while treatment with medical food was associated with less hypoglycemia (OR 0.352, CI 0.145-0.857, p=0.022). The linear regression model showed that metformin was associated with fewer hypoglycemic events (beta=-0.352 CI -1.391- -0.704, p<0.001). Nutrition was not found to be associated with the number of hypoglycaemic events., Conclusions: Treatment with oral nutrition supplements and metformin is associated with reduced incidence of hypoglycemia., Discussion: Oral nutrition is crucial for preventing hypoglycaemia during hospitalizations, regardless of the treatment for glucose control. Metformin is also beneficial.

Introduction: Hypoglycemia is a common occurrence in diabetic patients. But unlike non diabetic patients, its causes are frequently related to drugs they are receiving to control blood glucose. But this may not always be the case. Here we report a type 2 diabetic patient with severe hypoglycemia owing to acute hypopituitarism secondary to pituitary apoplexy., Case Presentation: A 45 year old male diabetic patient from Ethiopia taking 2 mg of oral glimepiride daily who presented with change in mentation of 30 minutes and blood glucose recording of 38 mg/dl upon arrival to the emergency room. Brain magnetic resonance imaging showed pituitary macroadenoma with hemorrhage suggestive of pituitary apoplexy. Blood work up showed low adrenocorticotropic hormone, cortisol, and serum sodium levels. Subsequently transsphenoidal hypophysectomy was done., Conclusion: The occurrence of hypoglycemia in a diabetic patient taking sulphonylurea monotherapy is common. But when it is severe enough to cause altered mentation, patients should be approached differently. In the presence of clinical clues suggesting cortisol deficiency, hypopituitarism can be a possible cause., (© 2024. The Author(s).)

Context: Insulinoma is a neuroendocrine tumor derived from pancreatic β -cells whose clinical manifestation is recurrent hypoglycemia. Insulinoma in a patient with preexisting diabetes is extraordinarily rare, and the unmasking of type 2 diabetes (T 2 DM) after insulinoma surgery is even rarer., Case Report: This article reports a 49-year-old male patient with insulinoma that masked the diagnosis of T 2 DM. The patient was admitted to the hospital with symptoms of hypoglycemia, such as repeated sweating, palpitations, and asthenia for over 4 years. The patient was diagnosed with insulinoma after completing relevant examinations. The emergence of hyperglycemia after the removal of insulinoma is attributable to the coexistence of T 2 DM. Surprisingly, a reversible decrease in cortisol levels was observed during the diagnostic process. We searched the previously published reports of this type of case from PubMed to determine why type 2 diabetes was covered by insulinoma and why glucocorticoids decreased., Conclusions: The diagnosis of T 2 DM in the patient after surgery may be related to increased food intake and insulin resistance induced by hyperinsulinemia caused by long-term hypoglycemia. The reversible decrease in cortisol levels, not adrenocortical insufficiency during the diagnostic process, may be caused by a transient abnormality in glucose counterregulation., (© 2024. The Author(s).)

Background: Diabetes mellitus (DM) is the most common metabolic disorder in pregnancy. Women with Type 2 DM seems to have no better perinatal outcomes than those with Type 1 DM., Methods: Single-center prospective cohort observational study. Pregnant women with diabetes (141 with Type 1 DM and 124 with Type 2 DM) that were followed in the university hospital between 2009 and 2021 were included in this study. Clinical data and obstetric and perinatal outcomes were collected., Results: As expected, women with Type 1 DM were younger and had a longer duration of diabetes than women with Type 2 DM. Obesity and chronic hypertension were higher in the group of women with Type 2 DM and their value of HbA1c in the second and third trimesters were lower than in Type 1 DM. No differences in prematurity were found, but more extreme prematurity was observed in Type 2 DM, as well as a higher rate of congenital malformations. The frequency of hypoglycemia and the weight of the newborn was higher in Type 1 DM. The maternal independent factors related to the weight of the newborn were: the glycemic control at the third trimester, the weight gain during pregnancy, and pregestational BMI., Conclusions: Newborns born to mothers with Type 1 DM were larger and had a higher frequency of hypoglycemia, while congenital malformations and precocious preterm was more associated to Type 2 DM. Metabolic control, weight gain and pregestational weight were important determinants of both obstetric and neonatal complications., (© 2024. The Author(s).)

Aim: The sympathetic nervous and hormonal counterregulatory responses to hypoglycaemia differ between people with type 1 and type 2 diabetes and may change along the course of diabetes, but have not been directly compared. We aimed to compare counterregulatory hormone and symptom responses to hypoglycaemia between people with type 1 diabetes, insulin-treated type 2 diabetes and controls without diabetes, using a standardised hyperinsulinaemic-hypoglycaemic clamp., Materials: We included 47 people with type 1 diabetes, 15 with insulin-treated type 2 diabetes, and 32 controls without diabetes. Controls were matched according to age and sex to the people with type 1 diabetes or with type 2 diabetes. All participants underwent a hyperinsulinaemic-euglycaemic-(5.2 ± 0.4 mmol/L)-hypoglycaemic-(2.8 ± 0.13 mmol/L)-clamp., Results: The glucagon response was lower in people with type 1 diabetes (9.4 ± 0.8 pmol/L, 8.0 [7.0-10.0]) compared to type 2 diabetes (23.7 ± 3.7 pmol/L, 18.0 [12.0-28.0], p < 0.001) and controls (30.6 ± 4.7, 25.5 [17.8-35.8] pmol/L, p < 0.001). The adrenaline response was lower in type 1 diabetes (1.7 ± 0.2, 1.6 [1.3-5.2] nmol/L) compared to type 2 diabetes (3.4 ± 0.7, 2.6 [1.3-5.2] nmol/L, p = 0.001) and controls (2.7 ± 0.4, 2.8 [1.4-3.9] nmol/L, p = 0.012). Growth hormone was lower in people with type 2 diabetes than in type 1 diabetes, at baseline (3.4 ± 1.6 vs 7.7 ± 1.3 mU/L, p = 0.042) and during hypoglycaemia (24.7 ± 7.1 vs 62.4 ± 5.8 mU/L, p = 0.001). People with 1 diabetes had lower overall symptom responses than people with type 2 diabetes (45.3 ± 2.7 vs 58.7 ± 6.4, p = 0.018), driven by a lower neuroglycopenic score (27.4 ± 1.8 vs 36.7 ± 4.2, p = 0.012)., Conclusion: Acute counterregulatory hormone and symptom responses to experimental hypoglycaemia are lower in people with type 1 diabetes than in those with long-standing insulin-treated type 2 diabetes and controls., (© 2024. The Author(s).)

Aims/introduction: To develop and validate a simple prediction model for hypoglycemia risk in patients with type 2 diabetes., Materials and Methods: We prospectively analyzed the data of 1,303 subjects in a third-class hospital in Tianjin and followed up their hypoglycemia events at 3 and 6 months. The hypoglycemia risk prediction models for 3 and 6 months were developed and the model performance was evaluated., Results: A total of 340 (28.4%) patients experienced hypoglycemia within 3 months and 462 (37.2%) within 6 months during the follow-up period. Age, central obesity, intensive insulin therapy, frequency of hypoglycemia in the past year, and hypoglycemia prevention education entered both model 3month and model 6month . The area under the receiver operating characteristic curve of model 3month and model 6month were 0.711 and 0.723, respectively. The Youden index was 0.315 and 0.361, while the sensitivities were 0.615 and 0.714, and the specificities were 0.717 and 0.631. The calibration curves showed that the models were similar to reality. The decision curves implied that the clinical net benefit of the model was clear., Conclusions: The study developed 3 and 6 month hypoglycemia risk prediction models for patients with type 2 diabetes. The discrimination and calibration of the two prediction models were good, and might help to improve clinical decision-making and guide patients to more reasonable self-care and hypoglycemia prevention at home., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Hypoglycemia, a prevalent acute complication among individuals with type 2 diabetes (T2D), manifests with varied symptoms. Those with diabetes who have previously encountered hypoglycemic episodes commonly develop a Fear of Hyperglycemia (FOH). Illness perception (IP) significantly affects self-care behaviors and health outcomes in individuals diagnosed with T2D., Objective: This study examined the correlation between IP and FOH among T2D patients and predictors of FOH., Methods: The present study employed a descriptive-analytical design. The target population for this investigation comprised patients diagnosed T2D who sought medical care at the clinic and endocrinology departments of a hospital affiliated with Alborz University of Medical Sciences. The data collection period spanned from August 2019 to March 2021. A total of 300 individuals were included in the sample. Questionnaires were administered to measure both IP and FOH. Statistical analysis was conducted to examine the association between IP and FOH, as well as to identify the predictors of FOH., Results: The results of the study indicated a statistically significant relationship between FOH and the mean score of IP among patients with diabetes (p = 0.001, r = 0.393), suggesting a moderate positive correlation between these variables. Additionally, the duration of illness, IP, and level of education were identified as variables that predicted FOH (p < 0.05)., Conclusion: The numerous factors that influence FOH in individuals diagnosed with T2D highlight the necessity for strategic planning and training initiatives aimed at enhancing IP and reducing FOH within this specific population. Healthcare providers should prioritize interventions that not only address patients' concerns but also contribute to the improvement of their overall well-being. By implementing such interventions, healthcare providers can optimize diabetes management strategies and ultimately enhance patient outcomes., (© 2024. The Author(s).)

Almost 90% of patients with type 2 diabetes mellitus (DM2) are obese. Obesity increases the risk of developing DM2 several times. The calculation of anthropometric indices is used to diagnose the severity of obesity, as well as to assess the risk associated with obesity. The aim of the study is to study the relationship between Body Mass Index (BMI), waist circumference to hip circumference ratio (waist-to-hip ratio, WC/HR), Body Roundness Index (BRI) and Visceral Adiposity Index (VAI) with the risk of hypoglycemia in elderly and senile patients with DM2. The study included 122 elderly and senile patients (mean age 71±6,18 years) with DM2. The study participants were divided into 2 groups: patients with cases of hypoglycemia (n=65) and patients without a history of hypoglycemia (n=57). We have found that lower BMI, WC/HR, BRI, and VAI values are significantly associated with an increased risk of hypoglycemia in patients with DM2 of older age groups.

Background and Aims: Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined., Materials and Methods: The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated individuals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA 1c ) was also evaluated. A random-effects meta-analysis was performed, and Hedges' g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ 2 estimate and I 2 statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias., Results: From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing individuals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA 1c was less in individuals with hypoglycaemia - 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ 2  = 0.2, I 2  = 54.3. No publication bias was evident., Conclusion: Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in individuals with post-bariatric surgery hypoglycaemia, while HbA 1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of individuals with hypoglycaemia following RYGB.PROSPERO Registration Number: CRD42021287515., (© 2023. Crown.)

Aims: To determine the clinical characteristics, risk factors and mortality outcomes associated with severe hypoglycaemia (SH) treated at a hospital emergency department., Materials and Methods: Adult patients presenting with SH to the Northern General Hospital, Sheffield, UK over a 44-month period were assessed for clinical characteristics, coexisting comorbidities and mortality outcomes, including cause of death, and analysed by age of diabetes onset, below and above age 40 years. Factors that predicted mortality were determined., Results: A total of 619 episodes of SH occurred in 506 individuals. Most had type 1 (T1D; n = 172 [34.0%]) or type 2 diabetes (T2D; n = 216 [42.7%]), but several attendees did not have diabetes (non-DM; n = 110 [21.7%]). Irrespective of age of diabetes onset, patients with T2D had more socioeconomic deprivation and comorbidities (P < 0.005). SH was uncommon in those with young-onset T2D, who constituted 7.2% of all episodes in diabetes. Hospital admission was high (60%-75%). The T2D cohort had the longest inpatient stay (median 5 days, vs. 2 and 3 days for the T1D and non-DM cohorts, respectively). Survival after the index SH episode was lower and mortality was higher in the non-DM (39.1%) and T2D (38.0%) cohorts than the T1D cohort (13.3%; all P < 0.05), with a median time to death of 13, 113 and 465 days, respectively. Most deaths (78%-86%) were from non-cardiovascular causes. Charlson index predicted mortality and poor survival in T1D and T2D (both P < 0.05)., Conclusions: Severe hypoglycaemia requiring emergency hospital treatment is associated with non-cardiovascular deaths and exerts a disproportionately greater impact on mortality in people with T2D and those without diabetes. Multimorbidity is an important risk factor for SH and increases mortality risk., (© 2023 John Wiley & Sons Ltd.)

Aim: Analysed clinical characteristics and influencing factors for hypoglycemia in hospitalized patients with type 2 diabetes mellitus (T2DM), and providing a scientific reference for precision nursing care of hypoglycemia in hospitalized patients with T2DM., Design: A cross-sectional study., Methods: This study involved 378 hospitalized patients diagnosed with T2DM who have suffered hypoglycemia. Through questionnaires and electronic medical records to obtain the data concerning the general information, clinical symptoms, all recorded blood glucose information, and the diabetes knowledge and self-management level of the patients. The clinical characteristics and influencing factors for hypoglycemia were analysed on the basis of the classification of hypoglycemia published by the American Diabetes Association in 2020., Results: Among 378 patients, 207 patients (54.76%) were experiencing Grade 1 hypoglycemia and 171 patients (45.24%) were experiencing Grade 2 hypoglycemia. Hypoglycemia and Grade 2 hypoglycemia in patients with T2DM occurred predominantly within the first 3 days of hospitalization. Hypoglycemia occurred most frequently after breakfast (74 cases, 19.6%), of which Grade 1 hypoglycemia and Grade 2 hypoglycemia accounted for 50%, respectively. Multivariable logistic regression identified risk factors for Grade 2 hypoglycemia in hospitalized patients with type 2 diabetes: older age, longer duration of diabetes, low body weight, diabetic nephropathy stages 4-5, diabetic autonomic neuropathy, inadequate self-management ability and diabetes knowledge, and lower educational background., Conclusions: Hypoglycemia in type 2 diabetes occurs in the first 3 days during the hospitalization and most often after breakfast during the full day. Identifying high-risk individuals and providing a scientific reference for precision nursing care of hypoglycemia in hospitalized patients with T2DM., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Aims: We aimed to develop and internally validate a real-world prognostic model for Level 3 hypoglycaemia risk compatible with outpatient care in the United States., Materials and Methods: iNPHORM is a 12-month, US-based panel survey. Adults (18-90 years old) with type 1 diabetes mellitus or insulin- and/or secretagogue-treated type 2 diabetes mellitus were recruited from a nationwide, probability-based internet panel. Among participants completing ≥ 1 follow-up questionnaire(s), we modelled 1-year Level 3 hypoglycaemia risk using Andersen and Gill's Cox survival and penalized regression with multiple imputation. Candidate variables were selected for their clinical relevance and ease of capture at point-of-care., Results: In total, 986 participants [type 1 diabetes mellitus: 17%; men: 49.6%; mean age: 51 (SD: 14.3) years] were analysed. Across follow-up, 035.1 (95% CI: 32.2-38.1)% reported ≥1 Level 3 event(s), and the rate was 5.0 (95% CI: 4.1-6.0) events per person-year. Our final model showed strong discriminative validity and parsimony (optimism corrected c-statistic: 0.77). Numerous variables were selected: age; sex; body mass index; marital status; level of education; insurance coverage; race; ethnicity; food insecurity; diabetes type; glycated haemoglobin value; glycated haemoglobin variability; number, type and dose of various medications; number of SH events requiring hospital care (past year and over follow-up); type and number of comorbidities and complications; number of diabetes-related health care visits (past year); use of continuous/flash glucose monitoring; and general health status., Conclusions: iNPHORM is the first US-based primary prognostic study on Level 3 hypoglycaemia. Future model implementation could potentiate risk-tailored strategies that reduce real-world event occurrence and overall diabetes burden., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To conduct a systematic review to summarize the definition, measurement tools, prevalence, and contributing factors of impaired awareness of hypoglycemia (IAH) in type 2 diabetes mellitus (T2DM)., Methods: A reproducible search strategy was used to identify factors affecting IAH in T2DM in PubMed, MEDLINE, EMBASE, Cochrane, PsycINFO, and CINAHL from inception until 2022. Literature screening, quality evaluation, and information extraction were performed independently by 2 investigators. A meta-analysis of prevalence was performed using Stata 17.0., Results: The pooled prevalence of IAH in patients with T2DM was 22% (95%CI:14-29%). Measurement tools included the Gold score, Clarke's questionnaire, and the Pedersen-Bjergaard scale. IAH in T2DM was associated with sociodemographic factors (age, BMI, ethnicity, marital status, education level, and type of pharmacy patients visited), clinical disease factors (disease duration, HbAlc, complications, insulin therapy regimen, sulfonylureas use, and the frequency and severity of hypoglycemia), and behavior and lifestyle (smoking and medication adherence)., Conclusion: The study found a high prevalence of IAH in T2DM, with an increased risk of severe hypoglycemia, suggesting that medical workers should take targeted measures to address sociodemographic factors, clinical disease, and behavior and lifestyle to reduce IAH in T2DM and thus reduce hypoglycemia in patients., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Aims: Acute kidney injury (AKI) is highly prevalent during hospitalization of patients with type 2 diabetes (T2D). We aimed to assess the impact of AKI and its severity and duration on the risk of hypoglycaemia in hospitalized patients with T2D., Methods: Retrospective cohort analysis of patients with T2D, admitted at a University Hospital in 2018-2019. AKI was defined as an increase in serum creatinine by ≥ 0.3 mg/dl (48 h) or ≥ 1.5 times baseline (7 days), and hypoglycaemia as blood glucose concentration < 70 mg/dl. Patients with chronic kidney disease stage ≥ 4 were excluded. We registered 239 hospitalizations with AKI and randomly selected 239 without AKI (control). Multiple logistic regression was used to adjust for confounding factors and ROC curve analysis to determine a cutoff for AKI duration., Results: The risk of hypoglycaemia was higher in the AKI group (crude OR 3.6, 95%CI 1.8-9.6), even after adjusting for covariates (OR 4.2, 95%CI 1.8-9.6). Each day of AKI duration was associated with a 14% increase in the risk of hypoglycaemia (95%CI 1.1-1.2), and a cutoff of 5.5 days of AKI duration was obtained for increased risk of hypoglycaemia and mortality. AKI severity was also associated with mortality, but showed no significant association with hypoglycaemia. Patients with hypoglycaemia had 4.4 times greater risk of mortality (95%CI 2.4-8.2)., Conclusions: AKI increased the risk of hypoglycaemia during hospitalization of patients with T2D, and its duration was the main risk factor. These results highlight the need for specific protocols to avoid hypoglycaemia and its burden in patients with AKI., (© 2023. The Author(s).)

Rationale: Hypoglycemia may cause diverse neurological manifestations, ranging from focal neurological deficits to irreversible coma. Severe and persistent hypoglycemia can lead to hypoglycemic encephalopathy (HE). Imaging findings of HE at different stages of 18F-FDG positron emission tomography/computed tomography (PET/CT) have rarely been reported. Herein, we describe a case of HE occurring in the medial frontal cortex, cerebellar cortex, and dentate nucleus using 18F-FDG PET/CT images from different periods. 18F-FDG PET/CT has a high value in displaying the lesion range and indicating the prognosis., Patient Concerns: A 57-year-old male patient with type 2 diabetes (T2D) was transferred to the hospital with a history of unconsciousness for 1 night. The patient showed a significant decrease in blood glucose levels., Diagnoses: The patient was initially diagnosed with a hypoglycemic coma., Interventions: The patient subsequently underwent a comprehensive treatment. The 18F-FDG PET/CT examination on the fifth day after admission revealed a significant symmetrical fluorodeoxyglucose (FDG)-positive accumulation in the bilateral medial frontal gyrus, cerebellar cortex, and dentate nucleus. A follow-up PET/CT examination 6 months later revealed hypometabolism in the bilateral medial frontal gyrus and no abnormalities in FDG uptake in the bilateral cerebellar cortex and dentate nucleus., Outcomes: The patient condition was stable 6 months later, with a slow response, memory deterioration, occasional dizziness, and episodes of hypoglycemia., Lessons: HE lesions with a high metabolic status may be related to a metabolic compensation mechanism in response to gray matter loss. Some of the more severely damaged cells eventually die even after the blood sugar levels return to normal. Less damaged nerve cells can be recovered. 18F-FDG PET/CT has high value in indicating the lesion range and prognosis of HE., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Previous studies have shown hypoglycaemia to be associated with an increased risk of dementia; however, there are several design challenges to consider. The objective of this study is to assess the association between hypoglycaemia and dementia while addressing these challenges using a lag period, exposure density sampling (EDS) and inverse probability of treatment weighting (IPTW)., Methods: This was a population-based cohort using data (1996-2018) from British Columbia, Canada. From a cohort of incident type 2 diabetes patients aged 40-70 years, we created a dynamic sub-cohort of hypoglycaemia-exposed (≥1 episode requiring hospitalization or a physician visit) and unexposed individuals using EDS, in which four unexposed individuals per one exposed were randomly selected into risk sets based on diabetes duration and age. Follow-up was until dementia diagnosis, death, emigration or 31 December 2018. Those diagnosed with dementia within 2 years of follow-up were censored. We adjusted for confounding using IPTW and estimated the hazard ratio (HR, 95% CI) of dementia using weighted conditional cause-specific hazards risk models with death as a competing risk., Results: Among 13 970 patients with incident type 2 diabetes, 2794 experienced hypoglycaemia. There were 329 dementia events over a median (interquartile range: IQR) follow-up of 5.03 (5.7) years. IPTW resulted in well-balanced groups with weighted incidence rates (95% CI) of 4.59 (3.52, 5.98)/1000 person-years among exposed and 3.33 (2.58, 3.88)/1000 person-years among unexposed participants. The risk of dementia was higher among those with hypoglycaemia (HR, 1.83; 95% CI 1.31, 2.57)., Conclusions: After addressing several methodological challenges, we showed that hypoglycaemia contributes to an increased risk of all-cause dementia among patients with type 2 diabetes., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Time spent in glycemic target range (time in range [TIR]; plasma glucose 70-180 mg/dL [3.9-10.0 mmol/L]) as a surrogate endpoint for long-term diabetes-related outcomes requires validation. This post hoc analysis investigated the association between TIR, derived from 8-point glucose profiles (derived TIR [dTIR]) at 12 months, and time to cardiovascular or severe hypoglycemic episodes in people with type 2 diabetes in the DEVOTE trial. At 12 months, dTIR was significantly negatively associated with time to first major adverse cardiovascular event ( P  = 0.0087), severe hypoglycemic episode ( P  < 0.0001), or microvascular event ( P  = 0.024). A nonsignificant trend was seen toward association between 12-month hemoglobin A1c (HbA1c) and these outcomes, but this was no longer seen after addition of dTIR to the model. The results support targeting TIR >70% and suggest dTIR could be used in addition to, or in some instances in place of, HbA1c as a clinical biomarker. Trial registration details: ClinicalTrials.gov, NCT01959529.

Background: A new IDF-DAR (International Diabetes Federation - Diabetes and Ramadan Alliance) risk stratification tool was published in 2021 to better stratify the risk of Ramadan fasting in people with diabetes., Methods: We performed a prospective, survey-based study before and after Ramadan 1442/2021 to explore the ability of the new IDF-DAR risk stratification tool to predict the probability of fasting and the risk of complications from fasting in people with diabetes., Results: A pre-Ramadan assessment was completed for 659 patients who intended to fast in Ramadan; 647(98.2%) answered the post-Ramadan follow-up questionnaire. Mean age was 53.5 years and 47.9% were females. 603(91.5%) had type 2 diabetes while 56(8.5%) had type 1 diabetes. Using the IDF-DAR risk criteria at the pre-Ramadan assessment, 339(51.4%) were categorized as low-risk (score <3), 173(26.3%) as moderate-risk (score 3.5-6) and 147(22.3%) as high-risk (score >6). 94.3%, 81.1% and 76.9% patients fasted the full 30 days in the low, moderate and high risk groups respectively (p < 0.0001). Any hypoglycaemia was reported in the low, moderate and high risk groups by 6.3%, 21.9% and 35.0% respectively while severe hypoglycaemia was reported by 3(2.1%) patients in the high, 3(1.8%) in the moderate and none(0%) in the low risk groups. Hyperglycaemia (>250 mg/dL) was reported in the low, moderate and high risk groups by 2.7%, 13.0% and 23.8% respectively., Conclusion: The new IDF-DAR risk assessment tool appears to reliably predict both the ability to fast during Ramadan as well as the likelihood of getting hypoglycaemia or hyperglycaemia., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols., Summary Background Data: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions., Methods: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001., Results: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses., Conclusions: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypoglycemia represents a risk for serious morbidity. We evaluated the prevalence and risk factors of hypoglycemia by continuous glucose monitoring (CGM) in patients with CKD with or without diabetes., Methods: In this cross-sectional study, outpatients with CKD stages G3-G5 (including hemodialysis) and type 2 diabetes without CKD were enrolled and underwent intermittently scanned CGM measurements for 7 days. The burden of CGM-measured hypoglycemia was assessed using the 7-day sum of area over the curve with glucose levels <70 mg/dl and the sum of time spent <54  mg/dl., Results: A total of 366 participants (148 participants with CKD and diabetes, 115 with CKD and without diabetes, and 103 without CKD and with diabetes) were included. Glucose levels of <54  mg/dl were observed in 41% of participants with CKD and diabetes, 48% of participants with CKD and without diabetes, and 14% of participants with diabetes and without CKD. However, only two participants reported hypoglycemic symptoms during CGM measurements, which were confirmed and documented by capillary blood glucose measurements. Between-group differences of 7-day area over the curve (<70 mg/dl) were as follows: hemodialysis group versus CKD stage G4 and G5 groups, -0.25 min·mg/dl per hour (95% confidence interval [CI], -6.40 to -0.59) P <0.001; CKD stage G4 and G5 groups versus CKD stage G3 group, -0.08 min·mg/dl per hour (95% CI, -0.0 to -0.50) P =0.15; and CKD stage G3 group versus diabetes without CKD group, -0.14 min·mg/dl per hour (95% CI, -0.0 to -0.20) P =0.01. In addition, the subgroup analysis of the diabetic or nondiabetic and at daytime or nighttime showed that the 7-day area over the curve (<70 mg/dl) and time spent (<54 mg/dl) was larger with worse kidney function., Conclusions: The lowering level of kidney function was strongly associated with the burden of hypoglycemia in patients with CKD., (Copyright © 2023 by the American Society of Nephrology.)

Background: Fasting during the holy month of Ramadan is one of the five pillars of Islam. Fasting is not meant to create excessive hardship on the Muslim individual according to religious tenets. It is important that health professionals are aware of potential risks associated with fasting during the month of Ramadan (mainly hypoglycemia and hyperglycemia)., Aims: To explore the impact of applying the principles of our 2020 recommendations for the management of type 2 diabetes (T2D) during the month of Ramadan., Methods: A multinational randomized controlled trial (RCT) was conducted in five Muslim majority countries. Six hundred and sixty participants were deemed eligible for the study; however, 23% declined to participate later for various reasons. In total, 506 participants were enroled and were equally randomized to the intervention or the control group. At the end of the study, data from 231 participants in the intervention group and 221 participants from the control group were collected after 12.6% and 8.7% were, respectively, lost to follow-up. Participants were randomized to receive a Ramadan-focussed education with treatment for diabetes adjusted as per our 2020 recommendation update compared with the local usual care (control group). Results are presented using mean, standard deviation, odds ratio (OR), and percentages., Results: At the end of the study, the number of hypoglycemic episodes in the intervention group was less than in participants who received usual care. The intervention group had significantly lower severe hypoglycemia compared to the control group with an OR of 0.2 [0.1-0.8]. Compared to baseline, both groups had a significant reduction in glycated haemoglobin (HbA1c), but the improvements were significantly greater in the intervention group. Whilst body weight reduced and high-density lipoprotein cholesterol increased with the intervention, these changes were not significantly different from usual care., Conclusions: A pre-Ramadan assessment of people with T2D coupled with pre-Ramadan education and an adjustment of glucose-lowering treatment as per our updated 2020 recommendations can prevent acute complications and allow a safer fast for people with T2D. We have shown that such an approach reduces the risk of developing severe hypoglycemia and improves the metabolic outcomes in people with T2D., (© 2022 John Wiley & Sons Ltd.)

Although promising therapeutics are in the pipeline, bariatric surgery (also known as metabolic surgery) remains our most effective strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Of the many available options, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are currently the most widely used procedures. RYGB and VSG have very different anatomical restructuring but both surgeries are effective, to varying degrees, at inducing weight loss and T2DM remission. Both weight loss-dependent and weight loss-independent alterations in multiple tissues (such as the intestine, liver, pancreas, adipose tissue and skeletal muscle) yield net improvements in insulin resistance, insulin secretion and insulin-independent glucose metabolism. In a subset of patients, post-bariatric hypoglycaemia can develop months to years after surgery, potentially reflecting the extreme effects of potent glucose reduction after surgery. This Review addresses the effects of bariatric surgery on glucose regulation and the potential mechanisms responsible for both the resolution of T2DM and the induction of hypoglycaemia., (© 2022. Springer Nature Limited.)

Objective: To examine the association between household food insecurity (HFI), glycemic control, severe hypoglycemia and diabetic ketoacidosis (DKA) among youth and young adults (YYA) with youth-onset type 2 diabetes., Research Design and Methods: This cross-sectional study included 395 YYA with type 2 diabetes from the SEARCH for Diabetes in Youth Study (2015-2019). HFI was reported by young adult participants or parents of minor participants via the US Household Food Security Survey Module. Glycemic control was assessed by HbA 1c and analyzed as a continuous and categorical variable (optimal: <7.0%, suboptimal: ≥7.0%-9.0%, poor: >9.0%). Acute complications included self-reported severe hypoglycemia or DKA in the last 12 months. Adjusted logistic and linear regression were used for binary and continuous outcomes, respectively., Results: Approximately 31% reported HFI in the past 12 months. Mean HbA 1c among those with HFI was 9.2% compared to 9.5% without HFI. Of those with HFI, 56% had an HbA 1c  >9.0% compared to 55% without HFI. Adjusted models showed no associations between HFI and glycemic control. Of those with HFI, 14.4% reported experiencing DKA and 4.7% reported severe hypoglycemia. YYA with HFI had 3.08 times (95% CI: 1.18-8.06) the odds of experiencing DKA as those without HFI. There was no association between HFI and severe hypoglycemia., Conclusions: HFI was associated with markedly increased odds of DKA but not with glycemic control or severe hypoglycemia. Future research among YYA with type 2 diabetes should evaluate longitudinally whether alleviating HFI reduces DKA., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Aims: This study assessed comparative effectiveness of glargine 300 U/mL (Gla-300) versus degludec 100 U/mL (Deg-100) in insulin-naïve patients with T2D., Methods: This is a retrospective, multicenter, non-inferiority study based on electronic medical records. All patients initiating Gla-300 or Deg-100 were 1:1 propensity score-matched (PSM). Linear mixed models were used to assess the changes in continuous endpoints. Incidence rates (IR) of hypoglycemia were compared using Poisson's regression models., Results: Nineteen centers provided data on 357 patients in each PSM cohort. HbA1c after 6 months (primary endpoint) decreased by - 1.70% (95%CI - 1.90; - 1.50) in Gla-300 group and - 169% (95%CI - 1.89; - 1.49) in Deg-100 group, confirming non-inferiority of Gla-300 versus Deg-100. Fasting blood glucose (BG) decreased by ~60 mg/dl in both groups; body weight remained unchanged. In both groups, the mean starting dose was 12U (0.15U/kg) and it was slightly titrated to 16U (0.20U/kg). IR (episodes per patient-months) of BG ≤70 mg/dl was 0.13 in Gla-300 group and 0.14 in Deg-100 group (p=0.87). IR of BG <54 mg/dL was 0.02 in both groups (p=0.49). No severe hypoglycemia occurred., Conclusion: Initiating Gla-300 or Deg-100 was associated with similar improvements in glycemic control, no weight gain and low hypoglycemia rates, without severe episodes during 6 months of treatment., (© 2022. The Author(s).)

Objective: An internally validated, one-year risk prediction model for severe hypoglycemia (SH) in type 2 diabetes was evaluated in a general hospital setting to externally verify and validate its performance., Research Design and Methods: Between December 2017 to December 2019, 2,645 adult patients with type 2 diabetes who visited the diabetes center were enrolled. The receiver operating characteristics curve and Harrell C-statistics were compared to identify the discrimination of the model. The predicted and actual incidence of SH for one year in the development and validation cohorts were compared by ranking participants by deciles of predicted risk., Results: The concordance index was 0.878 in the external validation cohort. The sensitivity and specificity of the predictive model were 0.833 and 0.847, respectively. Based on the predicted risk, we stratified the groups into four categories: low (<0.05%), intermediate (0.05% to <0.5%), high (0.5% to <2.0%), and very high-risk group (≥2.0%). The actual annual incidence of SH gradually increased with the increased risk score level for the decile group ( P for trend <0.001). The actual annual SH incidence significantly increased with increase in SH risk scores, which proportionately increased with age, duration of diabetes, glycated hemoglobin, and albuminuria and decreased with body mass index, renal function ( p for trends <0.001 for all) in type 2 diabetes., Conclusion: On external validation, the novel one-year SH prediction model showed excellent discrimination in participants with type 2 diabetes and can effectively screen high-risk patients for SH, even in the general hospital setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yun, Han, Choi, Cha, Ahn and Ko.)

Purpose: Since SGLT2 inhibitors may reduce postprandial hyperglycemia, this study aimed to evaluated whether empagliflozin might be useful in the treatment of postprandial hypoglycemia (PPH) postbariatric surgery (BS)., Patients and Methods: Fourteen patients who underwent BS, nine without type 2 diabetes and five with diabetes before surgery and in remission after surgery, were included. Seven of them presented symptoms of PPH (hypoglycemic group; HG) and seven were asymptomatic (nonhypoglycemic group (NHG)). A meal tolerance test was performed before and after administration of a daily dose of empagliflozin (EMPA) 25 mg for 3 days. Plasma glucose and serum insulin levels were measured., Results: In HG, compared with NHG, in the basal test, the area under the curve (AUC) of plasma glucose levels (AUCgly) was smaller (158.3 ± 25.3 vs 276.6 ± 79.2 mg h dL -1 ; p = 0.001) while the AUC of insulin levels (AUCins) did not differ, leading to a higher AUCins/AUCgly ratio (0.79 ± 0.46 vs 0.38 ± 0.20; p = 0.055) and a lower HOMA-IR (0.92 ± 0.22 vs 1.75 ± 0.77; p = 0.030). The HG after EMPA, but not the NHG, showed significant increases in glycemia leading to greater AUCgly (158.0 ± 25.3 to 197.2 ± 51.6 mg h dL -1 ; p = 0.043) without significant changes in AUCins. HOMA-IR increased only in the HG (0.92 ± 0.20 vs 1.61 ± 0.30; p = 0.025) and, when both groups were analyzed together, both before and post EMPA, a significant correlation was found between HOMA-IR and AUCgly values (r = 0.594; p = 0.002)., Conclusion: Our results suggest that empagliflozin increased glycemic levels in patients with PPH possibly through increases in hepatic glucose production., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To explore the safety and efficacy of 20% glucose solution in the treatment of adult diabetic patients with hypoglycemia., Methods: A non-randomized controlled paired design trial was conducted. The diabetes patients with hypoglycemia (blood glucose < 3.9 mmol/L) who were admitted to the department of endocrinology and metabolism of Affiliated Hospital of Jiangsu University from December 2020 to May 2021 were enrolled. When the patients developed hypoglycemia for the first time, 75 mL of 20% glucose solution was pumped intravenously at a constant speed within 15 minutes, which was named the 20% glucose solution group. When the patients had hypoglycemia again, 30 mL of 50% glucose solution was pumped intravenously at a constant speed within 3 minutes, which was named the 50% glucose solution group. If the blood glucose was still ≤ 3.9 mmol/L at 15 minutes of hypoglycemia treatment, or the patients were uncomfortable due to too fast drip speed, it should be terminated immediately. The hypoglycemia treatment should be handled according to the Chinese guidelines for the prevention and treatment of type 2 diabetes (2020 edition). The peripheral blood glucose level and the range of increase at 15 minutes of treatment, the success rate of one treatment, the peripheral blood glucose values at 60 minutes after successful hypoglycemia treatment, the incidence of phlebitis and exudation after hypoglycemia treatment, and the pain of local blood vessels in patients with hypoglycemia treatment were analyzed and compared between the two groups., Results: A total of 65 patients completed the treatment of hypoglycemia with 20% glucose solution and the success rate of one treatment was 100%. The peripheral blood glucose value at 15 minutes of hypoglycemia treatment was (8.30±1.37) mmol/L, and the increased range was (4.86±1.30) mmol/L. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment was (6.96±1.48) mmol/L, which indicated that 20% glucose solution could effectively increase blood glucose. Among 65 patients, 32 patients had hypoglycemia again, who were treated with 50% glucose solution, and the success rate of one treatment was 100%. When patients who received 50% glucose solution for hypoglycemia formed a paired design with the first 20% glucose solution treatment, the results showed that there was no significant difference in the peripheral blood glucose value and the increased range in blood glucose at 15 minutes of hypoglycemia treatment between the 20% glucose solution and the 50% glucose solution groups [peripheral blood glucose (mmol/L): 8.20 (7.70, 9.70) vs. 8.30 (7.80, 8.80), increase in blood glucose (mmol/L): 4.96±1.39 vs. 4.70±1.32, both P > 0.05], indicating that the glucose changing at 15 minutes of hypoglycemia treatment with 20% glucose solution was similar to that with 50% glucose solution. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment of 20% glucose solution group was significantly lower than that of 50% glucose solution group (mmol/L: 6.37±1.04 vs. 7.20±1.36, P < 0.01), which meant that the blood glucose tended to be more stable. There was no phlebitis and exudation after hypoglycemia treatment in both groups. The pain score of 20% glucose solution group was 0, however, 3 patients in 50% glucose solution group complained of local vascular pain, and the pain score was 1., Conclusions: 20% glucose solution can effectively treat hypoglycemia in diabetic patients, which has the same curative effect as 50% glucose solution and much safer. It can be used in patients with severe hypoglycemia.

Aim: To develop and validate a prediction model to evaluate the perioperative hypoglycemia risk in hospitalized type 2 diabetes mellitus (T2DM) patients undergoing elective surgery., Methods: We retrospectively analyzed the electronic medical records of 1410 T2DM patients who had been hospitalized and undergone elective surgery. Regression analysis was used to develop a predictive model for perioperative hypoglycemia risk. The receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test were used to verify the model., Results: Our study showed an incidence of 10.7% for level 1 hypoglycemia and 1.8% for level 2 severe hypoglycemia during the perioperative period. A perioperative hypoglycemic risk prediction model was developed that was mainly composed of four predictors: duration of diabetes ≥ 10 year, body mass index (BMI) < 18.5 kg/m 2 , standard deviation of blood glucose (SDBG) ≥ 3.0 mmol/L, and preoperative hypoglycemic regimen of insulin subcutaneous. Based on this model, patients were categorized into three groups: low, medium, and high risk. Internal validation of the prediction model showed high discrimination (ROC statistic = 0.715) and good calibration (no significant differences between predicted and observed risk: Pearson χ 2 goodness-of-fit P = 0.765)., Conclusions: The perioperative hypoglycemic risk prediction model categorizes the risk of hypoglycemia using only four predictors and shows good reliability and validity. The model serves as a favorable tool for clinicians to predict hypoglycemic risk and guide future interventions to reduce hypoglycemia risk., (© 2022. The Author(s).)

Background: Diabetes remission after bariatric surgery was reported to be characterized by increased risk of hypoglycemia., Objectives: This study aimed to examine the contribution of glycemic variability (GV) to the risk of hypoglycemia, and the suitability of time in range (TIR), an emerging glycemic marker, to define diabetes remission after Roux-en-Y gastric bypass (RYGB)., Setting: A single referral center in China., Methods: This retrospective study included 175 individuals with type 2 diabetes and obesity who underwent RYGB. Subjects were classified as remission/nonremission according to the current standard. Each participant underwent continuous glucose monitoring both before and 1 year after RYGB. GV was measured by glucose coefficient of variation (CV), and hypoglycemia was assessed by time below range (TBR)., Results: Complete remission was achieved in 88 of the 175 participants following RYGB. In the remission group, significant correlations between postoperative CV and TBRs (r = .353-.442, both P ≤ .001) were found. Excess hypoglycemia (TBR <54 , ≥1%, TBR <70, ≥4%) increased with ascending CV quintiles (both P for trend <.05) and was significantly more frequent in subjects with glucose CV >32.2% (both P <.05). Compared with glycated hemoglobin A1C, TIR showed stronger correlation with glucose CV and risk of hypoglycemia., Conclusion: Increased glycemic variability was linked to excess risk of hypoglycemia after RYGB. Furthermore, TIR may serve as a new metric, in addition to HbA1C, for defining diabetes remission., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Following bariatric surgery, patients can develop non-specific symptoms self-described as hypoglycemia. However, confirming hypoglycemia can be technically challenging, and therefore, these individuals are frequently treated empirically. This study aimed to describe what diagnostic evaluation and therapeutic interventions patients referred for post-bariatric surgery hypoglycemia undergo., Methods: Retrospective observational cohort study of patients with a history of bariatric surgery was evaluated for post-bariatric surgery hypoglycemia in a tertiary referral center from 2008 to 2017. We collected demographic and bariatric surgery information, clinical presentation of symptoms referred to as hypoglycemia, laboratory and imaging studies performed to evaluate these symptoms, and symptom management and outcomes., Results: A total of 60/2450 (2.4%) patients who underwent bariatric surgery were evaluated in the Department of Endocrinology for hypoglycemia-related symptoms. The majority were middle-aged women without type 2 diabetes who had undergone Roux-en-Y gastric bypass. Thirty-nine patients (65%) completed a biochemical assessment for hypoglycemia episodes. Six (10%) had confirmed hypoglycemia by Whipple's triad, and four (6.7%) met the criteria for post-bariatric surgery hypoglycemia based on clinical and biochemical criteria. All patients were recommended dietary modification as the initial line of treatment, and this intervention resulted in most patients reporting at least some improvement in their symptoms. Eight patients (13%) were prescribed pharmacotherapy, and two patients required additional interventions for symptom control., Conclusions: In our experience, evaluation for hypoglycemia-related symptoms after bariatric surgery was rare. Hypoglycemia was confirmed in the minority of patients. Even without establishing a diagnosis of hypoglycemia, dietary changes were a helpful strategy for symptom management for most patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Nocturnal asymptomatic hypoglycemia (NAH) is a serious complication of diabetes, but it is difficult to be detected clinically. This study was conducted to determine the largest amplitude of glycemic excursion (LAGE) to predict the episodes of NAH in outpatients with type 2 diabetes., Methods: Data were obtained from 313 outpatients with type 2 diabetes. All subjects received continuous glucose monitoring (CGM) for consecutive 72 hours. The episodes of NAH and glycemic variability indices (glucose standard deviation [SD], mean amplitude of plasma glucose excursion [MAGE], mean blood glucose [MBG]) were accessed via CGM. LAGE was calculated from self-monitoring blood glucose (SMBG)., Results: A total of 76 people (24.3%) had NAH. Compared to patients without NAH, patients with NAH showed higher levels of glucose SD (2.4 ± 0.9 mmol/L vs 1.7 ± 0.9 mmol/L, p <0.001), MAGE (5.2 ± 2.1 mmol/L vs 3.7 ± 2.0, p<0.001) and LAGE (4.6 ± 2.3 mmol/L vs 3.8 ± 1.9 mmol/L, p=0.007), and lower level of MBG (7.5 ± 1.5 mmol/L vs 8.4 ± 2.2 mmol/L, p=0.002). LAGE was significantly associated with the incidence of NAH and time below rang (TBR) in model 1 [NAH: 1.189 (1.027-1.378), p=0.021; TBR: 0.008 (0.002-0.014), p=0.013] with adjustment for age, BMI, sex, work, hyperlipidemia, complication and medication, and in model 2 [NAH: 1.177 (1.013-1.367), p=0.033; TBR: 0.008 (0.002-0.014), p=0.012] after adjusting for diabetes duration based on model 1, as well as in model 3 [NAH: 1.244 (1.057-1.464), p=0.009; TBR: 0.009 (0.002-0.016), p=0.007] with further adjustment for HbA1c based on model 2. In addition, no significant interactions were found between LAGE and sex, age, HbA1c, duration of diabetes, BMI and insulin therapy on the risk of NAH. The receiver operator characteristic (ROC) curve shows the ideal cutoff value of LAGE for the prediction of NAH was 3.48 mmol/L with 66.7% sensitivity, 50% specificity and 0.587 (95% CI: 0.509-0.665) of area under the ROC curve., Conclusions: High glycemic variability is strongly associated with the risk of NAH. The LAGE based on SMBG could be an independent predictor of NAH for outpatients with type 2 diabetes, and LAGE greater than 3.48 mmol/L could act as a warning alarm for high risk of NAH in daily life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Tan, Wu, Shen, Huang, Wang, Liu, Song, Lin, Shi and Li.)

Type 2 diabetes mellitus is the leading cause of end stage renal disease. Chronic kidney disease (CKD) especially end stage renal disease (ESRD) usually require renal replacement therapy and are on maintenance dialysis. Glycemic control is challenging in ESRD because of uremia. Patients of ESRD commonly experience hypoglycemia during hemodialysis and these hypoglycemic episodes are most commonly seen in diabetic CKD patients. The number of hypoglycemic episodes increase mortality and morbidity in CKD patients. Hence it is important to prevent these hypoglycemic episodes during dialysis in CKD patients with diabetes., Objectives: To study occurrence of hypoglycemia in patients of diabetic chronic kidney disease and effect of corrective measures to prevent hypoglycemia., Material: In this study we measured Random blood sugar and dialysate sugar level before dialysis and during dialysis. This both sugar levels are measured at 30 min, 90 min and 120 min interval from start of dialysis by GOD POD method. The patients who had hypoglycemia during dialysis were provided with intradialytic carbohydrate rich snack and insulin dose reduced by 0.2-0.3 units/kg for next setting of hemodialysis., Observation: A total of 200 diabetic CKD patients were included in the study.93(46.5%)patients developed hypoglycemia in the first setting, out of them 48 (51.61%) patients were not on any medication,33(35.48%) people on insulin, 12 (12.9%) patients on OHA. Mean blood sugar levels in patients who had hypoglycemia of the first setting was significantly low as compared to patients who did not have hypoglycemia (p value &lt; 0.05) After corrective measures, in the second setting (n=93) of hemodialysis only 14(15%)people showed hypoglycemia out of them 07 (50%) people were not on any medication, 5 (36%) on insulin, 2 (14%) on OHA. Mean blood sugar levels of patients who had hypoglycemia in the second setting was low as compared to those without hypoglycemia but the difference was not significant. (p value &gt; 0.05).No deaths reported during study., Conclusion: 1. The occurrence of hypoglycemia in diabetic CKD patients during hemodialysis is significant. 2. The corrective measures are effective in preventing hypoglycemia during hemodialysis. 3. Insulin therapy and oral hypoglycemic agents should therefore be used with caution in patients of hemodialysis., (© Journal of the Association of Physicians of India 2011.)

Aim: To identify evidence-based risk factors for major complications during Ramadan fasting in people with diabetes grouped under IDF-DAR risk categories., Methods: This prospective observational multicenter study was conducted by Baqai Institute of Diabetology and Endocrinology (BIDE) between April-June 2019. People with diabetes having intention to fast during Ramadan were recruited. Demographic data collection along with risk categorization was done during pre-Ramadan visit. Structured education was given on one- to-one basis to each of the study participants. Assessment of complications was done during post Ramadan visit., Results: A total of 1045 people with diabetes participated with near equal gender distribution. Two thirds of study population was grouped into very high- and high-risk categories. Frequencies of major hypoglycemia, major hyperglycemia, hospitalization & need to break the fast were 4.4%, 10.8%, 0.8% & 3.1% respectively. On multivariate analysis, the risk factors found for major hypoglycemia during Ramadan were male gender, use of sedatives & antidepressants & having type1 diabetes mellitus, history of DKA/HHS during last 3 months for major hyperglycemia, major hypoglycemia & hospitalization for breaking of fast while older age, acute illness, and major hypoglycemia were identified factors for hospitalization., Conclusion: In this prospective study evidence-based risk factors for fasting related major complications were identified in people with diabetes. It is imperative to recognize these factors during pre-Ramadan risk assessment visit., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A 79-year-old woman with type 2 diabetes receiving insulin was rushed to our hospital due to severe hypoglycemia. Glucose was administered, and the consciousness disturbance was promptly improved. A few hours later, conjugate deviation of the eyes to the right and left hemiplegia occurred at a normal glucose level. Cerebral magnetic resonance imaging (MRI) showed hyperintensities of the right posterior limb of the internal capsule and the medial thalamus on diffusion-weighted imaging sequences. However, the changes observed using MRI disappeared completely on the third day, and her symptoms subsequently improved. This may have been a case of glucose reperfusion injury.

Aims/introduction: Strict management of glucose levels in elderly people with diabetes or with comorbidities exposes them to the risk of severe hypoglycaemia (capillary or venous glucose ≤3.3 mmol/L) and the associated morbidity and mortality. We aimed to describe the clinical, laboratory, and epidemiological characteristics of people with diabetes admitted to the Emergency Department in Cayenne, French Guiana for severe hypoglycaemia and identify avoidable behaviours in this population., Materials and Methods: An observational epidemiological study of adults with diabetes who presented to the Emergency Department with severe hypoglycaemia was conducted between 2015 and 2018. Their medical history, clinical and laboratory data were collected. The primary outcome was the association between therapeutic misuse and age ≥65 years., Results: Overall, 178 admissions were analysed. The main cause of hypoglycaemia was insulin dosing-error or inappropriate glycaemic targets. Among those ≥65 years, 59% had a glycated haemoglobin ≤48 mmol/mol (6.5%), and the median duration of their diabetes was 20 years. Among them, 60% were treated with sulfonylurea, repaglinide, biphasic insulin, or mixed drugs, and 48% were on non-diabetes related treatments that had a hypoglycaemic effect. Furthermore, 23% of the elderly treated with oral antidiabetics had chronic kidney disease., Conclusion: Many avoidable risk factors for severe hypoglycaemia have been highlighted, in particular insulin dosing errors or non-compliance with recommendations for participants ≥ 65 years. Primary care physicians and homecare nurses need to provide preventive interventions and undergo training., (© 2021 Diabetes UK.)

Importance: Social determinants of health play a role in diabetes management and outcomes, including potentially life-threatening complications of severe hypoglycemia and diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS). Although several person-level socioeconomic factors have been associated with these complications, the implications of area-level socioeconomic deprivation are unknown., Objective: To examine the association between area-level deprivation and the risks of experiencing emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises (ie, DKA or HHS)., Design, Setting, and Participants: This cohort study used deidentified administrative claims data for privately insured individuals and Medicare Advantage beneficiaries across the US. The analysis included adults with diabetes who met the claims criteria for diabetes between January 1, 2016, and December 31, 2017. Data analyses were performed from November 17, 2020, to November 11, 2021., Exposures: Area deprivation index (ADI) was derived for each county for 2016 and 2017 using 17 county-level indicators from the American Community Survey. ADI values were applied to patients who were living in each county based on their index dates and were categorized according to county-level ADI quintile (with quintile 1 having the least deprivation and quintile 5 having the most deprivation)., Main Outcomes and Measures: The numbers of emergency department visits or hospitalizations related to the primary diagnoses of hypoglycemia and DKA or HHS (ascertained using validated diagnosis codes in the first or primary position of emergency department or hospital claims) between 2016 and 2019 were calculated for each ADI quintile using negative binomial regression models and adjusted for patient age, sex, health plan type, comorbidities, glucose-lowering medication type, and percentage of White residents in the county., Results: The study population included 1 116 361 individuals (563 943 women [50.5%]), with a mean (SD) age of 64.9 (13.2) years. Of these patients, 343 726 (30.8%) resided in counties with the least deprivation (quintile 1) and 121 810 (10.9%) lived in counties with the most deprivation (quintile 5). Adjusted rates of severe hypoglycemia increased from 13.54 (95% CI, 12.91-14.17) per 1000 person-years in quintile 1 counties to 19.13 (95% CI, 17.62-20.63) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.41 (95% CI, 1.29-1.54; P < .001). Adjusted rates of DKA or HHS increased from 7.49 (95% CI, 6.96-8.02) per 1000 person-years in quintile 1 counties to 8.37 (95% CI, 7.50-9.23) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.12 (95% CI, 1.00-1.25; P = .049)., Conclusions and Relevance: This study found that living in counties with a high area-level deprivation was associated with an increased risk of severe hypoglycemia and DKA or HHS. The concentration of these preventable events in areas of high deprivation signals the need for interventions that target the structural barriers to optimal diabetes management and health.

Aim: To conduct a systematic review of published studies reporting on the longitudinal impacts of hypoglycaemia on quality of life (QoL) in adults with type 2 diabetes., Method: Database searches with no restrictions by language or date were conducted in MEDLINE, Cochrane Library, CINAHL and PsycINFO. Studies were included for review if they used a longitudinal design (e.g. cohort studies, randomised controlled trials) and reported on the association between hypoglycaemia and changes over time in patient-reported outcomes related to QoL., Results: In all, 20 longitudinal studies published between 1998 and 2020, representing 50,429 adults with type 2 diabetes, were selected for review. A descriptive synthesis following Synthesis Without Meta-analysis guidelines indicated that self-treated symptomatic hypoglycaemia was followed by impairments in daily functioning along with elevated symptoms of generalised anxiety, diabetes distress and fear of hypoglycaemia. Severe hypoglycaemic events were associated with reduced confidence in diabetes self-management and lower ratings of perceived health over time. Frequent hypoglycaemia was followed by reduced energy levels and diminished emotional well-being. There was insufficient evidence, however, to conclude that hypoglycaemia impacted sleep quality, depressive symptoms, general mood, social support or overall diabetes-specific QoL., Conclusions: Longitudinal evidence in this review suggests hypoglycaemia is a common occurrence among adults with type 2 diabetes that impacts key facets in the physical and psychological domains of QoL. Nonetheless, additional longitudinal research is needed-in particular, studies targeting diverse forms of hypoglycaemia, more varied facets of QoL and outcomes assessed using hypoglycaemia-specific measures., (© 2021 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Purpose: Few studies have reported on self-monitored blood glucose changes following acute exercise, particularly in patients with type 2 diabetes prescribed oral sulfonylureas and insulin medication. This study sought to determine the magnitude of post-exercise blood glucose changes and incidence of hypoglycemia (blood glucose < 4.0 mmol/L) in relation to medication regimen., Methods: A retrospective chart review was conducted in adults with type 2 diabetes attending a 6-month rehabilitation program. Demographics, medications, exercise prescription and patient-reported pre/post-BG values were collected at program initiation. It was hypothesized that patients with type 2 diabetes will experience a post-exercise capillary blood glucose reduction (ΔcapBG), and that incidents of hypoglycemia (< 4.0 mmol/L) will be strongly associated with insulin or oral secretagogue class of medication., Results: A chart review was conducted (n = 52, 46.2% males, mean age: 62.7 ± 8.3 years, A1c: 7.7 ± 1.6%, body mass index, BMI: 34.4 ± 7.8 kg/m 2 ) in patients with type 2 diabetes (9.0 ± 7.7 years since diagnosis). A greater reduction in BG was related to a greater pre-exercise BG (beta [95% CI]: - 0.46 [- 0.54, - 0.37] mmol, p < 0.0001), independent of BMI and exercise duration. Post-exercise hypoglycemia (< 4.0 mmol) was associated with prescribed insulin use (vs. non-users: 14.5% vs. 3.0%, p < 0.05). Among insulin users, pre-mixed insulin had the highest incidence of hypoglycemia (vs. non-users: 50% vs. 3%, p < 0.0001) and insulin (bolus and basal; vs. non-users: 11.1% vs. 3%, p = 0.04)., Conclusions: These findings may suggest a low post-exercise hypoglycemia occurrence in patients with type 2 diabetes, except when taking insulin. Self-management strategies should be considered, especially for patients on insulin medications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims/hypothesis: Out-of-hospital hypoglycaemia is a common complication for individuals with diabetes mellitus and represents a significant burden to emergency medical services (EMS). We aim to identify the factors associated with receiving parenteral treatment and hospital conveyance., Methods: We retrospectively analysed a 6-month data set of all London EMS hypoglycaemia. Individuals with a known diabetes diagnosis were included in our analysis and stratified as either having type 1 diabetes or type 2 diabetes., Results: A total of 2862 incidents occurred within the area served by London Ambulance Service between January and June 2018. Fifty percent of incidents required parenteral treatment (intravenous glucose or intramuscular glucagon) and were conveyed to hospital. A higher arrival of blood glucose, intact consciousness and receiving oral glucose treatment were all negative predictors for requiring parenteral therapy. Forty-three percent of incidents were labelled as 'hypoglycaemia' by the EMS call handler, and greater odds of hospitalisation were observed among incidents that received parenteral treatment (OR 2.52 [95% CI 1.46, 4.33] p < 0.01) and individuals with type 2 diabetes (OR 2.67 [95% CI 1.52, 4.71] p < 0.01). Repeated callouts from 2% (n = 50) of individuals accounted for 10% (286) of all incidents attended, and 56.4% of individuals attended by EMS on more than one occasion had type 1 diabetes., Conclusions/interpretation: Severe hypoglycaemia requiring emergency service attendance remains common, as does the requirement for parenteral therapy and conveyance to hospital. Early intervention, education and improved accessibility to risk prevention strategies may reduce the necessity for emergency parenteral treatment and hospitalisation, especially among individuals suffering from recurrent hypoglycaemia and high-risk individuals with type 2 diabetes., (© 2021 Diabetes UK.)

Background: Insulinomas are rare clinical entities, but concurrent diabetes mellitus is even more uncommon, and the combination is easily missed. Recurrent hypoglycemia could be misconstrued as improved glycemic control. We present an unusual patient with type 2 diabetes and neuroglycopenia, with apparent improved glycemic control due to an insulinoma., Case Presentation: A 54-year-old mixed ancestry man with a positive family history of type 2 diabetes mellitus was diagnosed with type 2 diabetes mellitus and hypertension 8 years prior to admission. He presented with episodes of abnormal behavior and hypoglycemia. Inappropriately high insulin and C-peptide concentrations were identified at the time of hypoglycemia. Despite poor adherence to his diabetic treatment, he had no target organ damage relating to diabetes, and his hemoglobin A1c (HbA1c) was 5.3%. A diagnosis of insulinoma was made, and he was started on diazoxide, with endoscopic ultrasound revealing a possible lesion in the pancreatic tail measuring 12 mm × 12 mm. A fine-needle aspiration biopsy could not be performed due to overlying splenic arteries and the risk of vascular perforation. An intraoperative ultrasound confirmed a 15 mm × 10 mm tumor in the pancreatic tail, necessitating a partial pancreatectomy and splenectomy, which were curative. A well-differentiated intermediate grade 2 pancreatic neuroendocrine tumor producing insulin was confirmed on histopathology., Conclusions: Recurrent, progressive hypoglycemia and improved glycemic control in a diabetic, without an alternative explanation, may suggest an insulinoma. Insulinomas that exist with type 1 diabetes mellitus, particularly malignant insulinomas, must have escaped autoimmune attack through lack of autoantigen expression. Computed tomography on its own may be insufficiently sensitive for diagnosis of insulinomas, whereas endoscopic and intraoperative ultrasonography may improve the identification of the culprit lesion., (© 2021. The Author(s).)

Background: We investigated the uses and frequency of self-monitoring of blood glucose (SMBG) with glycemic control and hypoglycemia in two groups of type 2 diabetes (T2D) (recently diagnosed and long-term follow-up) using real-world data in Taiwan (the Taiwan Diabetes Registry)., Methods: Patients with T2D recently diagnosed within 6 months (n = 3297, mean age 54.4 ± 13.9 years) and T2D patients with long-term follow-up (n = 1201, mean age 65.5 ± 12.1 years, mean diabetes duration 14.3 ± 7.8 years) from the Taiwan Diabetes Registry were analysed. All patients were interviewed by certified diabetes educators. Information about SMBG and hypoglycemia was recorded. Demography, personal history, and laboratory data were obtained from electronic medical records. Logistic regression analyses were used to examine the associations of SMBG with glycated haemoglobin (HbA1c) <7% and hypoglycemia., Results: Mean HbA1c values were 8.4 ± 2.5 and 7.6 ± 1.4%, respectively, in the recently diagnosed and long-term follow-up T2D groups. The self-reported rates of hypoglycemic events within 3 months were 10.5% and 19.0%, respectively. SMBG was associated with higher odds of HbA1c <7% (OR 1.21, 95% CI 1.01-1.44) in patients with recently diagnosed T2D, but with lower odds of HbA1c <7% in T2D patients with long-term follow-up (OR 0.60, 95% CI 0.44-0.82). In both study populations, SMBG was independently associated with hypoglycemia (OR 3.90 [95% CI 2.99-5.08] and OR 3.93 [95% CI 2.73-5.66], respectively). The aforementioned findings were consistent across the strata of SMBG frequency., Conclusion: We reported different associations between SMBG and glycemic control in patients recently diagnosed with T2D and in T2D patients with long-term follow-up. SMBG was associated with higher detection of hypoglycemic episodes in both study populations., (© 2021 John Wiley & Sons Ltd.)

Objective: There is a high risk of asymptomatic hypoglycemia associated with hemodialysis (HD) using glucose-free dialysate; therefore, the inclusion of glucose in the dialysate is believed to prevent intradialytic hypoglycemia. However, the exact glycemic fluctuation profiles and frequency of asymptomatic hypoglycemia using dialysates containing >100 mg/dL glucose have not been determined., Research Design and Methods: We evaluated the glycemic profiles of 98 patients, 68 of whom were men, with type 2 diabetes undergoing HD (HbA 1c 6.4 ± 1.2%; glycated albumin 20.8 ± 6.8%) with a dialysate containing 100, 125, or 150 mg/dL glucose using continuous glucose monitoring., Results: Sensor glucose level (SGL) showed a sustained decrease during HD, irrespective of the dialysate glucose concentration, and reached a nadir that was lower than the dialysate glucose concentration in 49 participants (50%). Twenty-one participants (21%) presented with HD-related hypoglycemia, defined by an SGL <70 mg/dL during HD and/or between the end of HD and their next meal. All these hypoglycemic episodes were asymptomatic. Measures of glycemic variability calculated using the SGL data (SD, coefficient of variation, and range of SGL) were higher and time below range (<70 mg/dL) was lower in participants who experienced HD-related hypoglycemia than in those who did not, whereas time in range between 70 and 180 mg/dL, time above range (>180 mg/dL), HbA 1c , and glycated albumin of the two groups were similar., Conclusions: Despite the use of dialysate containing 100-150 mg/dL glucose, patients with diabetes undergoing HD experienced HD-related hypoglycemia unawareness frequently. SGL may fall well below the dialysate glucose concentration toward the end of HD., (© 2021 by the American Diabetes Association.)

Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP-4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium-glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP-4 is efficient in these populations. This mini-review highlights the islet mechanisms of DPP-4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP-4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background and Aims: Blinded retrospective continuous glucose monitoring (rCGM) provides detailed information about real-life glycaemic profile. In persons with type 2 diabetes without adequate glycaemic control, the structured introduction of rCGM may be beneficial to sustain improvements in diabetes management., Methods and Results: 102 individuals with insulin-treated type 2 diabetes, age less than 66 years old and HbA1c >7.5%, were recruited. Participants performed a 7-day blinded rCGM (iPro2) every four months for one year. Biochemical, anthropometric, and rCGM data was collected. Participants' and healthcare professionals' perceptions were assessed. 90 participants completed the protocol. HbA1c was 9.1 ± 0.1% one year prior to enrolment and 9.4 ± 0.1% at enrolment (p < 0.01). With the rCGM-based intervention, a decrease in HbA1c was achieved at 4 months (8.4 ± 0.1%, p < 0.0001), and 12 months (8.1 ± 0.1%, p < 0.0001). A significant increase in time-in-range was observed (50.8 ± 2.4 at baseline vs 61.5 ± 2.2% at 12 months, for 70-180 mg/dL, p < 0.001), with no difference in exposure time to hypoglycaemia. After 12 months, there was an increase in self-reported diabetes treatment satisfaction (p < 0.05)., Conclusion: In persons with type 2 diabetes and poor metabolic control, specific data from blinded rCGM informed therapeutic changes and referral to targeted education consultations on nutrition and insulin administration technique. Therapeutic changes were made more frequently and targeted to changes in medication dose, timing, and/or type, as well as to lifestyle. Together, these brought significant improvements in clinical outcomes, effective shared decision-making, and satisfaction with treatment., Registration Number: NCT04141111., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: There is very limited information about glycemic control after discharge from the ICU. The aims of this study were to evaluate the prevalence of hypoglycemia in ICU survivors with type-2 diabetes and determine whether hypoglycemia is associated with cardiac arrhythmias., Design: Prospective, observational, two-center study. Participants underwent up to 5 days of simultaneous blinded continuous interstitial glucose monitoring and ambulatory 12-lead electrocardiogram monitoring immediately after ICU discharge during ward-based care. Frequency of arrhythmias, heart rate variability, and cardiac repolarization markers were compared between hypoglycemia (interstitial glucose ≤ 3.5 mmol/L) and euglycemia (5-10 mmol/L) matched for time of day., Setting: Mixed medical-surgical ICUs in two geographically distinct university-affiliated hospitals., Patients: Patients with type-2 diabetes who were discharged from ICU after greater than or equal to 24 hours with greater than or equal to one organ failure and were prescribed subcutaneous insulin were eligible., Measurements and Main Results: Thirty-one participants (mean ± sd, age 65 ± 13 yr, glycated hemoglobin 64 ± 22 mmol/mol) were monitored for 101 ± 32 hours post-ICU (total 3,117 hr). Hypoglycemia occurred in 12 participants (39%; 95% CI, 22-56%) and was predominantly nocturnal (40/51 hr) and asymptomatic (25/29 episodes). Participants experiencing hypoglycemia had 2.4 ± 0.7 discrete episodes lasting 45 minutes (interquartile range, 25-140 min). Glucose nadir was less than or equal to 2.2 mmol/L in 34% of episodes. The longest episode of nocturnal hypoglycemia was 585 minutes with glucose nadir less than 2.2 mmol/L. Simultaneous electrocardiogram and continuous interstitial glucose monitoring recordings were obtained during 44 hours of hypoglycemia and 991 hours of euglycemia. Hypoglycemia was associated with greater risk of bradycardia but did not affect atrial or ventricular ectopics, heart rate variability, or cardiac repolarization., Conclusions: In ICU survivors with insulin-treated type-2 diabetes, hypoglycemia occurs frequently and is predominantly nocturnal, asymptomatic, and prolonged., Competing Interests: Dr. Ali Abdelhamid’s institution received funding from the Intensive Care Foundation and Baxter; she disclosed that Welch Allyn Australia loaned Holter recorders for the conduct of the study but was not involved in the design, conduct, analysis, or reporting of the study; and she was supported by a Royal Adelaide Hospital A. R. Clarkson Scholarship. Dr. Bernjak received support for article research from the Intensive Care Foundation. Drs. Bernjak’s, Summers’, and Heller’s institutions received funding from an Intensive Care Foundation grant, administered by Melbourne Health. Dr. Phillips was supported by a Royal Adelaide Hospital Early Career Fellowship. Dr. Heller received funding from NovoNordisk, Eli Lilly, Zealand Pharma, Sanofi, Aventis, and Astra Zeneca. Dr. Deane is supported by a National Health and Medical Research Council Career Development Fellowship. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs)., Methods and Findings: The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%)., Conclusions: This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions., Competing Interests: The authors have declared that no competing interests exist.

Background: As a common medical emergency in individuals with diabetes, hypoglycemia events can impose significant demands on hospital resources. Based on diabetes patients with and without hypoglycemia, we assess the cost of hypoglycemic events on China's hospital system., Method: Our study sample comprised 7110 diabetes episodes, including 1417 patients with hypoglycemia (297 patients with severe and 1120 with non-severe hypoglycemia) and 5693 diabetes patients without hypoglycemia. Data on patient social-demographics, length of hospital stay, and hospitalization costs were collected on each patient from Health Information System in Shandong province, China. The additional hospital costs caused by hypoglycemia were assessed by the cost difference between diabetes patients with and without hypoglycemia, including severe and non-severe hypoglycemia. China-wide hospital costs of hypoglycemia were estimated based on adjusted additional hospital costs, comprising inspection, treatment, drugs, materials, nursing, general medical costs, and other costs, caused by hypoglycemia, the prevalence of diabetes and hypoglycemia events, and the rates of hospitalization. Multiple sensitivity analyses were conducted to assess the impact of variations in the key input parameters on the primary estimates., Results: Total hospital costs for patients with hypoglycemia (US$3020.61) were significantly higher than that of patients without hypoglycemia (US$1642.91). The average additional cost caused by hypoglycemia was US$1377.70, with higher average costs of US$1875.89 for severe hypoglycemia and lower average costs of US$1244.76 for non-severe hypoglycemia. The additional hospital cost caused by severe and non-severe hypoglycemia patients was higher for the 60 to 75 year old group, married patients and patients accessing free medical services. Generally, hypoglycemic patients with Urban and Rural Resident Basic Medical Insurance incurred higher additional hospital costs than patients with Urban Employees Basic Medical Insurance. Based on these estimates, the total annual additional hospital costs arising from hypoglycemia events in China were estimated to be US$67.52 million. Sensitivity analyses suggested that the costs of hypoglycemia events ranged up to US$49.99 million to 67.52 million., Conclusion: : Hypoglycemic events imposed a substantial cost on China's hospital system, with certain subgroups of patients, such as older patients and those with free health insurance, using medical resources more intensively to treat hypoglycemia events. We recommend more effective planning of prevention and treatment regimes for hypoglycemia patients; further reform to China's health insurance schemes; and better hospital cost control for those accessing free hospital services., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: This study investigated the hypoglycemia risk in people with type 2 diabetes (T2D) who initiated or switched to insulin glargine 300 U/mL (Gla-300) by stratifying them by age and renal function., Methods: We examined data from 4621 people with T2D (1227 insulin-naïve and 3394 insulin-experienced) of the X-STAR study, a prospective, observational, 12-month study conducted from December 2015 to August 2018 in Japan. Participants were stratified by age (<65, 65 to <75, and ≥75 years) and estimated glomerular filtration rate (eGFR) (≥90, 60 to <90, 30 to <60, and <30 mL/min/1.73 m 2 ). Hypoglycemia was defined according to the Ministry of Health, Labour and Welfare manual of Japan., Results: No apparent increase in the proportion of people who experienced hypoglycemia was found in all subgroups. The proportions were 2.9-3.5% and 2.7-5.2% of insulin-naïve and insulin-experienced people, respectively, for age subgroups, and 2.4-4.7% and 4.6-4.8%, respectively, for eGFR subgroups. The result was similar for HbA1c levels below and at or above 7.0% in all age subgroups., Conclusions: Our study found no apparent increase in the hypoglycemia risk in people with older age and renal impairment who were administered Gla-300. These results would provide reassuring information on Gla-300 use., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T Hirose received honoraria from Sanofi K.K., Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company, Ltd., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Mitsubishi Tanabe Pharma Corp., and Kowa Company, Ltd.; research funding from Mitsubishi Tanabe Pharma Corp. and AstraZeneca K.K.; and subsidies or donations from Astellas Pharma Inc., Novartis Pharma K.K., Eli Lilly Japan K.K., MSD K.K., Sanofi K.K., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Company, Ltd., Taisho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Soiken, Inc., and Bayer Yakuhin, Ltd. M Odawara received honoraria, subsidies, or donations from Novo Nordisk Pharma Ltd., Sanofi K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., Astellas Pharma Inc., AstraZeneca K.K., Kowa Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company, Ltd., Mitsubishi Tanabe Pharma Corp., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd. M Matsuhisa received honoraria from Sanofi K.K., Takeda Pharmaceutical Company, Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Corp., Astellas Pharma Inc., Novo Nordisk Pharma Ltd., and MSD K.K.; research funding from Sysmex Corp., Nissui Pharmaceutical Co., Ltd., and Tokushima Data Service Co. Ltd.; and subsidies or donations from Astellas Pharma Inc., Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp., Novartis Pharma K.K., Sanofi K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company, Ltd., MSD K.K., and Ono Pharmaceutical Co., Ltd. R Koshida and M Senda are employees of Sanofi K.K. Y Tanaka serves in an advisory role to Top Corp.; and received honoraria from MSD K.K., Kissei Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Company, Ltd., Arkray, Inc., and Sanofi K.K.: collaborative research funding from Nichirei Foods Inc.; and subsidies or donations from Sanofi K.K., Takeda Pharmaceutical Company, Ltd., MSD K.K., Daiichi Sankyo Co., Ltd., Novo Nordisk Pharma Ltd., Kissei Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Arkray, Inc., AstraZeneca K.K., Mitsubishi Tanabe Pharma Corp., Ono Pharmaceutical Co., Ltd., and Astellas Pharma Inc. Y Terauchi received honoraria from Astellas Pharma Inc., AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly Japan K.K., Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corp., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sanofi K.K., Taisho Toyama Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Company, Ltd.; and research funding or grant from AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly Japan K.K., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., and Sanofi K.K. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)