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Aims: Type 2 diabetes (T2D) and its complications disproportionally affect American Indian and Alaska Native (AI/AN) peoples. Prescribing decisions for anti‐diabetic medications are complicated and require balancing medication benefits, costs and side effects. Little is known about trends in anti‐diabetic medication use as well as acute diabetes complications among AI/AN adults. Here, we examined patterns and trends in anti‐diabetic medication use and rates of hospital admissions or emergency department (ED) visits due to severe hypoglycaemia and hyperglycaemia among AI/AN adults with T2D. Materials and Methods: We conducted a retrospective analysis of Indian Health Service (IHS) Improving Health Care Delivery Data Project. A total of 39 183 AI/AN adults aged ≥18 years with T2D who used IHS or Tribal health services during any of the fiscal years (FYs) 2009–2013 were included. Utilization rates of each class of anti‐diabetic medications and rates of severe hypoglycaemia and severe hyperglycaemia in emergency room and/or inpatient discharge diagnoses were calculated for each year. Longitudinal statistical models were fitted to examine time trends of anti‐diabetic medication use and complications. Results: During 2009–2013, use of metformin (56.0%–60.5%), insulin (31.4%–35.9%) and dipeptidyl peptidase‐4 inhibitors (1.4%–9.0%) increased, whereas the use of sulfonylureas (40.3%–32.9%) and thiazolidinediones (TZDs, 31.6%–8.8%) decreased significantly. Trends in severe hypoglycaemia (1.6%–0.8%) and severe hyperglycaemia (2.0%–1.6%) declined gradually. Conclusions: There were significant changes in the utilization of different anti‐diabetic medication classes during 2009–2013 among AI/AN adults with T2D. Concurrently, there were significant reductions in severe hypoglycaemia and severe hyperglycaemia. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions To determine the prognosis associated with severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) in adults presenting to a hospital emergency department (ED).Medical records of adults with type 1 (T1D) and type 2 (T2D) diabetes who attended the ED with SH and DKA between 1 January 2019 and 30 June 2023, were reviewed for comorbidities, long‐term survival, mortality and causes of death.A total of 429 episodes of DKA occurred in 293 people and 643 episodes of SH in 515 people. DKA predominated in T1D (77.6%) and SH in T2D (54.3%). In T2D, 32.3% of DKA events were associated with sodium‐glucose cotransporter‐2 inhibitor (SGLT2‐i) medication. In both SH and DKA, patients with T2D were older and had more comorbidities than T1D, particularly cardiorenal disease, heart failure, cognitive impairment and cancer (all p < 0.005). Compared with T1D, mortality was higher in T2D after SH (48.4% vs. 19.9%, p < 0.005) and after DKA (30.8% vs. 13.4%, p = 0.001) with shorter median times to fatal outcome (SH: 134 vs. 511 days; DKA: 43 vs. 266 days, both p < 0.005). Long‐term survival was lower (p < 0.005) and mortality risk was higher in T2D after index presentation with SH (HR 3.43 [95% CI: 2.43–4.84], p < 0.005) and DKA (HR 3.00 [95% CI: 1.77–5.10], p < 0.005). Irrespective of diabetes type, most causes of death in SH and DKA were non‐cardiovascular.SH and DKA events requiring hospital treatment herald a poor prognosis with greater mortality in T2D adults with multimorbidity. A significant number of DKA episodes in T2D occurred in people receiving SGLT2‐i medication. [ABSTRACT FROM AUTHOR]

Aims: We aim to compare and correlate Gold and Clarke questionnaire scores with hypoglycaemic symptomatic responses between insulin‐treated type 2 diabetes participants with and without IAH in a real‐life study. Methods: Insulin‐treated type 2 diabetes participants attending an outpatient diabetes clinic in Singapore were asked to complete the Gold and Clarke questionnaires, record capillary blood glucose (CBG) and hypoglycaemic symptoms for 4 weeks. Results: Data were collected from 153 participants (M:F = 98:55) with mean age 61.0 ± 9.4 years, duration of diabetes 19.5 ± 8.8 years and HbA1c 68 ± 17 mmol/mol (8.4 ± 1.5%). Gold and Clarke methods classified 19.6% and 26.8% of participants with IAH, respectively. Using CBG threshold of <3 mmol/L, significantly greater proportion of participants with intact awareness were experiencing autonomic symptoms than those with IAH with either method (Gold: 69% vs. 18%, p = 0.006; Clarke: 85% vs. 46%, p = 0.010). Significantly greater proportion of participants with IAH experienced no hypoglycaemia symptoms than those with intact awareness (Gold: 3.4% vs. 36%, p = 0.015; Clarke: 3.7% vs. 31%, p = 0.031). Participants with IAH had significantly higher rates of severe hypoglycaemia in the preceding year compared to those without (Gold: 17% vs. 3.3%; Clarke: 15% vs. 2.7%, p = 0.012). Conclusions: Gold and Clarke questionnaires are appropriate tools in ascertaining IAH status in insulin‐treated type 2 diabetes participants. This is the first time whereby the hypoglycaemia symptomology has robustly validated the Gold and Clarke questionnaire in insulin‐treated type 2 diabetes participants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this review was to identify and review studies reporting on the epidemiological, social and economic impact associated with severe hypoglycaemia (SH) in people with diabetes mellitus (DM) in Portugal. Methods: A structured literature search was carried out in PubMed and Embase using a predefined selection criterion. Studies published in either Portuguese or English, between January 2010 and February 2021 were deemed eligible for inclusion. Results: Twelve studies including adults (aged ≥ 18 years) with type 1 and/or type 2 diabetes mellitus (T1DM/T2DM) were eligible for inclusion. Epidemiological estimates varied according to the setting and type of data source used. The proportion of patients who experienced ≥ 1 SH episode (SHE) in the previous 6–12 months varied from 3.1% in adults with T2DM to 36.8% in adults with T1DM. In adults with T2DM the prevalence in a community-based study was highest in the insulin and secretagogue combination treated group (9.1%), while in an emergency department setting prevalence was highest in the insulin-based therapy group and the oral hypoglycaemic agent without secretagogues group (32.0% and 20.0%, respectively). The prevalence of SH in other studies in patients with DM ranged from 0.1% (emergency department) to 18.1% (hospital ward). Patients treated with secretagogues had the highest rates of hospitalisations. In patients with T1DM, the annual rate of SHE was higher in those with impaired hypoglycaemia awareness than in those with intact awareness. Mean total cost (direct and indirect) per SHE ranged from €1493.00 in patients with T2DM treated in an emergency setting to €2608.51 in patients with T1DM who were hospitalised. Conclusion: Hypoglycaemic events, especially SHE, have a significant effect on the life of persons living with DM and their caregivers. Studies show that the prevalence of this acute complication of diabetes is not negligible. In addition to the negative impact on the quality of life, the burden of SHE in Portugal translates into a significant impact on the global health expenditure. [ABSTRACT FROM AUTHOR]

Background Bariatric surgery has been widely indicated for the management of obesity and related comorbidities. However, there are uncertainties pertaining to the risks of post-bariatric severe hypoglycaemia (SH), cardiovascular diseases (CVDs), end-stage kidney diseases (ESKDs) and all-cause mortality in obese patients with Type 2 diabetes mellitus (T2DM), especially among Asian populations. Methods A retrospective population-based cohort of 1702 obese T2DM patients who were free of CVD and ESKD were assembled based on the 2006–17 Hospital Authority database. One-to-five propensity-score matching was used to balance baseline covariates between patients in bariatric surgery and control groups. Incidence rates (IRs) of SH, CVD, Stage 4/5 chronic kidney diseases (CKD), ESKD and all-cause mortality events for two groups were calculated. Hazard ratios (HR) for SH, CVD and Stage 4/5 CKD events were assessed using Cox-proportional hazard models. Changes in estimated glomerular filtration rate (eGFR) and urine albumin–creatinine ratio (UACR) were measured up to 60 months. Results Over a mean follow-up period of 32 months with 5725 person-years, cumulative incidences of mortality, CVD, Stage 4/5 CKD, ESKD and SH were 0, 0.036, 0.050, 0.017 and 0.020, respectively. The surgery group had a significant reduction in risk of CVD events (HR = 0.464, P = 0.015) and no occurrence of mortality events. However, there were no significant differences in risks of SH [HR = 0.469, 95% confidence interval (CI): 0.204–1.081], Stage 4/5 CKD (HR =0.896, 95% CI: 0.519–1.545) and ESKD (HR = 0.666, 95% CI: 0.264–1.683) between two groups, although IRs were lower in the surgery group. Surgical patients had significantly higher eGFR within 12 months and had significantly lower UACR until 48 months. Conclusions Among obese T2DM patients, bariatric surgery lowered the risk of CVD and mortality, and was beneficial towards the kidney outcomes. [ABSTRACT FROM AUTHOR]

Aims: The ability to differentiate patient populations with type 2 diabetes at high risk of severe hypoglycaemia could impact clinical decision making. The aim of this study was to develop a risk score, using patient characteristics, that could differentiate between populations with higher and lower 2‐year risk of severe hypoglycaemia among individuals at increased risk of cardiovascular disease. Materials and methods: Two models were developed for the risk score based on data from the DEVOTE cardiovascular outcomes trials. The first, a data‐driven machine‐learning model, used stepwise regression with bidirectional elimination to identify risk factors for severe hypoglycaemia. The second, a risk score based on known clinical risk factors accessible in clinical practice identified from the data‐driven model, included: insulin treatment regimen; diabetes duration; sex; age; and glycated haemoglobin, all at baseline. Both the data‐driven model and simple risk score were evaluated for discrimination, calibration and generalizability using data from DEVOTE, and were validated against the external LEADER cardiovascular outcomes trial dataset. Results: Both the data‐driven model and the simple risk score discriminated between patients at higher and lower hypoglycaemia risk, and performed similarly well based on the time‐dependent area under the curve index (0.63 and 0.66, respectively) over a 2‐year time horizon. Conclusions: Both the data‐driven model and the simple hypoglycaemia risk score were able to discriminate between patients at higher and lower risk of severe hypoglycaemia, the latter doing so using easily accessible clinical data. The implementation of such a tool (http://www.hyporiskscore.com/) may facilitate improved recognition of, and education about, severe hypoglycaemia risk, potentially improving patient care. [ABSTRACT FROM AUTHOR]

Aims: To undertake a post‐hoc analysis, utilizing a hypoglycaemia risk score based on DEVOTE trial data, to investigate if a high risk of severe hypoglycaemia was associated with an increased risk of cardiovascular events, and whether reduced rates of severe hypoglycaemia in patients identified as having the highest risk affected the risk of cardiovascular outcomes. Materials and Methods: The DEVOTE population was divided into quartiles according to patients' individual hypoglycaemia risk scores. For each quartile, the observed incidence and rate of severe hypoglycaemia, major adverse cardiovascular event (MACE) and all‐cause mortality were determined to investigate whether those with the highest risk of hypoglycaemia were also at the greatest risk of MACE and all‐cause mortality. In addition, treatment differences within each risk quartile [insulin degludec (degludec) vs. insulin glargine 100 units/mL (glargine U100)] in terms of severe hypoglycaemia, MACE and all‐cause mortality were investigated. Results: Patients with the highest risk scores had the highest rates of severe hypoglycaemia, MACE and all‐cause mortality. Treatment ratios between degludec and glargine U100 in the highest risk quartile were 95% confidence interval (CI) 0.56 (0.39; 0.80) (severe hypoglycaemia), 95% CI 0.76 (0.58; 0.99) (MACE) and 95% CI 0.77 (0.55; 1.07) (all‐cause mortality). Conclusions: The risk score demonstrated that a high risk of severe hypoglycaemia was associated with a high incidence of MACE and all‐cause mortality and that, in this high‐risk group, those treated with degludec had a lower incidence of MACE. These observations support the hypothesis that hypoglycaemia is a risk factor for cardiovascular events. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is characterised by chronic hyperglycaemia and variable degrees of insulin deficiency and resistance. Hyperglycaemia and elevated fatty acids exert harmful effects on β-cell function, regeneration and apoptosis (gluco-lipotoxicity). Furthermore, chronic hyperglycaemia triggers a vicious cycle of insulin resistance, low-grade inflammation and a cascade of pro-atherogenic processes. Thus, timely near to normal glucose control is of utmost importance in the management of type 2 diabetes and prevention of micro- and macroangiopathy. The majority of patients are multimorbid and obese, with critical comorbidities such as cardiovascular disease, heart failure and chronic kidney disease. Recently published guidelines therefore recommend patient-centred risk/benefit-balanced use of oral glucose-lowering drugs or a glucagon-like peptide 1 (GLP-1) receptor agonist, or switching to insulin with glycated haemoglobin (HbA1c) out of target. This article covers the indications of early insulin treatment to prevent diabetes-related complications, particularly in subgroups with severe insulin deficit, and to achieve recovery of residual β-cell function. Furthermore, the individualised, risk/benefit-balanced, timely initiation of insulin as second and third option is analysed. Timely insulin initiation may prevent diabetes progression, reduce diabetes-related complications and has less serious adverse effects. Basal insulin is the preferred option in most clinical situations with consequences of undertreatment of chronic hyperglycaemia. [ABSTRACT FROM AUTHOR]

Some therapies for diabetes increase the risk of hypoglycaemia, in particular all insulins and insulin secretagogues, including the glinides and sulfonylureas. Hypoglycaemia remains a major limiting factor to successful glycaemic management, despite the availability of prevention options such as insulin analogues, continuous glucose monitoring, insulin pumps, and dogs that have been trained to detect hypoglycaemia. Non‐severe (self‐treated) and severe (requiring assistance for recovery) hypoglycaemia rates are higher in people with type 1 diabetes, but those with insulin‐treated type 2 diabetes are also at risk. Education and regular review are essential between people with diabetes and their caregivers and healthcare professionals about symptoms, prevention and treatment. Awareness of the potential dangers of hypoglycaemia is fundamental to the optimal management of diabetes. When therapy is intensified to achieve glycaemic targets, it is important that people at risk of severe hypoglycaemia, and particularly their caregivers, have ready access to effective treatment for hypoglycaemia emergencies. The current and potential formulations of glucagon available for treatment of severe hypoglycaemia are reviewed. [ABSTRACT FROM AUTHOR]

Aim: To determine the incidence of severe hypoglycaemia and its predictors in community‐based patients with type 2 diabetes studied between 2008 and 2013 compared with those in a cohort of patients with type 2 diabetes from the same geographical area assessed a decade earlier. Methods: We studied 1551 participants (mean age 65.7 years, 51.9% men) with type 2 diabetes from the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). Severe hypoglycaemia was ascertained as that requiring ambulance attendance, emergency department services and/or hospitalization. Cox proportional hazards modelling was used to determine predictors of a first episode of severe hypoglycaemia, and negative binomial regression was used to identify predictors of frequency. Results: Sixty‐three participants (4.1%) experienced 83 episodes, representing an incidence of 1.34/100 participant‐years (95% confidence interval [CI] 1.08 to 1.67; vs 1.67/100 participant‐years [95% CI 1.31‐2.13] in the Fremantle Diabetes Study Phase I [FDS1]; P = 0.18). Those experiencing severe hypoglycaemia experienced one to four episodes in both cohorts. The independent predictors of incident severe hypoglycaemia in the FDS2 were: older age; higher educational attainment; alcohol consumption; current smoking; sulphonylurea/insulin treatment; prior severe hypoglycaemia; renal impairment; and plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). The same variables except smoking were associated with frequency of severe hypoglycaemia. Most of these risk factors paralleled those in the FDS1, but current smoking and plasma NT‐proBNP were novel. Conclusions: The incidence and frequency of severe hypoglycaemia did not change between the Fremantle Diabetes Study phases but novel risk factors, including plasma NT‐proBNP, were observed in the FDS2. [ABSTRACT FROM AUTHOR]

Aims: This study was conducted to investigate potential link between type 2 diabetes mellitus (T2DM) and epilepsy, and the role of severe hypoglycaemia (SH) might play in the relationship.Methods: This was a cohort study based on Taiwan's National Health insurance claims. Totally 751,792 people with T2DM and 824,253 matched controls were identified in 2002-2003 and followed to incidence of epilepsy or end of 2011. We used Cox proportional hazard model to relate epilepsy incidence to separate and joint effects of T2DM and SH. A possible mediation effect of SH on the association between T2DM and epilepsy was analyzed.Results: Over a 10-year follow-up, patients with T2DM had a higher incidence rate of epilepsy than controls (35.0 vs 21.9 per 10,000 person-years). After controlling for potential confounders including SH, T2DM increased the hazard of epilepsy by some 50%. The stratified analysis further indicated that T2DM (hazard ratio (HR)=1.44, 95% confidence interval (CI) = 1.40-1.47), and SH (HR = 2.22, 95% CI = 1.76-2.81) were both independent risk factors for epilepsy. SH did not modify but mediated 12% of the association between T2DM and epilepsy.Conclusion: Our findings supported that SH may increase the risk of epilepsy, and that T2DM may increase risk of epilepsy independent of SH. [ABSTRACT FROM AUTHOR]

Objective. To study one-year incidence and risk factors of severe hypoglycaemias (SH) in adult drug-treated diabetic patients living in two Finnish communities. Design. The episodes of SH and their risk factors were identified from local ambulance registers, from the databases of local health care units, and from patient questionnaires. Setting. The target population consisted of all drug-treated diabetic patients from the two middle-sized communities in southern Finland, altogether 1776 patients. The study was retrospective. Subjects. A total of 1469 patients (82.7% of the target population) gave informed consent for the use of their medical records and 1325 patients (74.6% of the target population) returned the detailed 36-item questionnaire. Results. Of type 1 and type 2 insulin-treated diabetic patients, 14.6% and 1.0%, respectively, needed ambulance or emergency room care (incidence of 30.5 and 3.0 per 100 patient years). However, 31.0% of type 1 and 12.3% of type 2 diabetic patients reported at least one episode of SH (incidence of 72.0 and 27.0 per 100 patient years). Of all insulin-treated patients, 53 (7.8%) reported three or more episodes of SH. Significant independent risk factors for SH were depression, daily exercise, and nephropathy but not glycaemic control. Conclusion. The incidence of SH was high in both types of insulin-treated diabetic patients. However, the recurrent episodes of SH were clustered in a small minority of insulin-treated patients with diabetes. The risk of SH should be considered when assessing the treatment target for an individual diabetic patient. [ABSTRACT FROM AUTHOR]

Aims: Real-world evidence of the safety of insulin degludec compared with insulin glargine U100 is sparse. This study sought to investigate the risk of major cardiovascular events, severe hypoglycaemia, and all-cause mortality after initiation of degludec or glargine U100 in the population of Denmark.Materials and Methods: All Danish people with diabetes initiating treatment on degludec (n=5159) or glargine (n=4041) in 2016 to 2017 were included in the study. The effect of insulin treatment on the endpoints of major cardiovascular events, severe hypoglycaemia, and all-cause mortality was analysed with Cox proportional hazard models. The models were adjusted for age, sex, diabetes duration, diabetes type, highest completed education, and annual income. The model of severe hypoglycaemia was also adjusted for severe hypoglycaemia prior to baseline. The model of mortality was also adjusted for history of alcohol abuse, use of antidepressants, use of opioids, and use of anxiolytics. Lastly, the models of major cardiovascular events and mortality were also adjusted for Charlson comorbidity index.Results: Use of degludec resulted in an almost twofold decrease in risk of death (hazard rate [HR]: 0.54, 95% CI: 0.44-0.65) compared with use of glargine. No statistically significant risk changes were found for major cardiovascular events (HR: 0.86, 95% CI: 0.62-1.19) and severe hypoglycaemia (HR: 1.13, 95% CI: 0.66-1.93). The proportion of cause of death due to malignant neoplasm of pancreas was almost doubled for glargine compared with degludec.Conclusions: These results indicate that insulin degludec has a safer profile with respect to all-cause mortality as compared with insulin glargine U100. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The DEVOTE study compared the cardiovascular safety of two basal insulins, degludec, and glargine U100 in patients with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). In this review, we summarize the results of DEVOTE and provide a clinical perspective.Recent Findings: DEVOTE was a phase 3b, multicenter, international, treat-to-target, double-blind, event-driven trial. Patients with T2D > 50 years of age with prior CVD or > 60 years of age with CVD risk factors were randomly assigned to receive either degludec (n = 3818) or insulin glargine U100 (n = 3819) and were followed until at least 633 positively adjudicated major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) accrued. At baseline, the mean age of the subjects was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean HbA1c was 8.4 ± 1.7%. After a median follow-up of 2 years, HbA1c had decreased to 7.5 ± 1.2% in each group. Degludec was non-inferior to insulin glargine U100 with respect to the primary MACE outcome (hazard ratio 0.91; 95% CI 0.78-1.06). Significantly, lower rates of severe hypoglycemia and nocturnal severe hypoglycemia were observed with degludec compared to glargine U100 (rate ratios of 0.60; 95% CI 0.48-0.76 and 0.47; 95% CI 0.31 to 0.73, respectively). DEVOTE demonstrated that the cardiovascular safety of degludec was comparable to that of insulin glargine U100 in patients with T2D at high risk for CVD. Additionally, degludec was superior to insulin glargine U100 with respect to the risk for severe hypoglycemia. These results suggest that degludec might be preferred in patients at risk for severe hypoglycemia, including the elderly, those with CVD and/or those with chronic kidney disease. [ABSTRACT FROM AUTHOR]