Search

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: 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]

Aims: To assess if the risk of all‐cause mortality increases in people with type 1 diabetes (T1D) with increasing number of severe hypoglycaemia episodes requiring hospitalization. Materials and methods: We conducted a national retrospective observational cohort study in people with T1D (diagnosed between 2000 and 2018). Clinical, comorbidity and demographic variables were assessed for impact on mortality for people with no, one, two and three or more episodes of severe hypoglycaemia requiring hospitalization. The time to death (all‐cause mortality) from the timepoint of the last episode of severe hypoglycaemia was modelled using a parametric survival model. Results: A total of 8224 people had a T1D diagnosis in Wales during the study period. The mortality rate (95% confidence interval [CI]) was 6.9 (6.1‐7.8) deaths/ 1000 person‐years (crude) and 15.31 (13.3‐17.63) deaths/ 1000 person‐years (age‐adjusted) for those with no occurrence of severe hypoglycaemia requiring hospitalization. For those with one episode of severe hypoglycaemia requiring hospitalization the mortality rate (95% CI) was 24.9 (21.0‐29.6; crude) and 53.8 (44.6‐64.7) deaths/ 1000 person‐years (age‐adjusted), for those with two episodes of severe hypoglycaemia requiring hospitalization it was 28.0 (23.1‐34.0; crude) and 72.8 (59.2‐89.5) deaths/ 1000 person‐years (age‐adjusted), and for those with three or more episodes of severe hypoglycaemia requiring hospitalization it was 33.5 (30.0‐37.3; crude) and 86.3 (71.7‐103.9) deaths/ 1000 person years (age‐adjusted; P < 0.001). A parametric survival model showed that having two episodes of severe hypoglycaemia requiring hospitalization was the strongest predictor for time to death (accelerated failure time coefficient 0.073 [95% CI 0.009‐0.565]), followed by having one episode of severe hypoglycaemia requiring hospitalization (0.126 [0.036‐0.438]) and age at most recent episode of severe hypoglycaemia requiring hospitalization (0.917 [0.885‐0.951]). Conclusions: The strongest predictor for time to death was having two or more episodes of severe hypoglycaemia requiring hospitalization. [ABSTRACT FROM AUTHOR]

Aim: Several risk factors for severe hypoglycaemia (SH) are associated with insulin‐treated diabetes. This study explored potential risk factors in adults with insulin‐treated type 2 diabetes mellitus (T2DM). Materials and Methods: In this case‐control study, adults with T2DM initiating insulin were identified in the IQVIA PharMetrics® Plus database. The index date was the date of the first SH event (cases). Using incidence‐density sampling, controls were selected from those who had been exposed 'at risk' of SH for the same amount of time as each case. After exact‐matching on the well‐established factors, previously unreported risk factors were evaluated through conditional logistic regression. Results: In 3153 case‐control pairs, pregnancy [odds ratios (OR) = 3.20, p =.0003], alcohol abuse (OR = 2.43, p <.0001), short‐/rapid‐acting insulin (OR = 2.22/1.47, p <.0001), cancer (OR = 1.87, p <.0001), dementia/Alzheimer′s disease (OR = 1.73, p =.0175), peripheral vascular disease (OR = 1.59, p <.0001), antipsychotics (OR = 1.59; p =.0059), anxiolytics (OR = 1.51, p =.0012), paralysis/hemiplegia/paraplegia (OR = 1.51, p =.0416), hepatitis (OR = 1.50, p =.0303), congestive heart failure (OR = 1.47, p =.0002), adrenergic‐corticosteroid combinations (OR = 1.45, p =.0165), β‐adrenoceptor agonists (OR = 1.40, p =.0225), opioids (OR = 1.38, p <.0001), corticosteroids (OR = 1.35, p =.0159), cardiac arrhythmia (OR = 1.29. p =.0065), smoking (OR = 1.28, p =.005), Charlson Comorbidity Index score 2 (OR = 1.28, p =.0026), 3 (OR = 1.41, p =.0016) or ≥4 (OR = 1.57, p =.0002), liver/gallbladder/pancreatic disease (OR = 1.26, p =.0182) and hypertension (OR = 1.19, p =.0164) were independently associated with SH. Conclusions: Although all people with insulin‐treated diabetes are at risk of SH, these results have identified some previously unrecognized risk factors and sub‐groups of insulin‐treated adults with T2DM at greater risk. Scrutiny of current therapies and comorbidities are advised as well as additional glucose monitoring and education, when identifying and managing SH in vulnerable populations. [ABSTRACT FROM AUTHOR]

The beneficial effects of closed-loop insulin delivery in patients with highly unstable type 1 diabetes eligible for islet transplantation are maintained over 6 months: An extension study of the DBLHU-WP10 trial Prospective analysis of satisfaction and usability of closed-loop Diabeloop DBLHU treatment in patients with highly unstable type 1 diabetes. Keywords: artificial pancreas; brittle diabetes; closed-loop; hypoglycaemia unawareness; problematic hypoglycaemia; severe hypoglycaemia; type 1 diabetes; unstable diabetes EN artificial pancreas brittle diabetes closed-loop hypoglycaemia unawareness problematic hypoglycaemia severe hypoglycaemia type 1 diabetes unstable diabetes 956 961 6 04/07/22 20220501 NES 220501 PEER REVIEW The peer review history for this article is available at https://publons.com/publon/10.1111/dom.14654. Insulin delivery DBLHU system DBLHU is a hybrid, CL insulin delivery system combining a Dexcom G6 CGM device, a Kaleido insulin pump and the investigational DBLHU software into a dedicated controller handset. [Extracted from the article]

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]

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]

Aims: Severe hypoglycaemia is associated with a high risk of cardiovascular events in patient with diabetes. The aim of this study was to clarify the temporal relationship between hypoglycaemia and cardiovascular events. Materials and methods: This observational cohort study was conducted using Taiwan's Longitudinal Cohort of Diabetes Patients Database, which included 360 000 patients with newly diagnosed diabetes during the period 1999 to 2001. Patients with the first severe hypoglycaemia after 2002 served as the study cohort. Each patient in the study cohort was matched with two control patients without severe hypoglycaemia, based on a propensity score. A joinpoint regression model was used to determine trends in all‐cause mortality and incidence of cardiovascular disease (CVD) events in both cohorts. Results: A total of 10 157 patients with severe hypoglycaemia and 20 314 matched controls were recruited. Patients with severe hypoglycaemia had a significantly higher risk of CVD (HR, 7.28; 95% CI, 5.19–10.20) and all‐cause mortality (HR, 19.92; 95% CI, 13.42–29.56) during the first month compared with those without. In patients with severe hypoglycaemia, the incidence of CVDs dropped by 17.29% monthly during the first 4 months and slowly decreased (−0.67%) during subsequent months. All‐cause mortality decreased by 16.55% and 3.24% monthly during months 0–6 and months 6–17, respectively. Conclusions: Severe hypoglycaemia is associated with a greater risk of cardiovascular events and death, especially during the first month following a hypoglycaemic episode. Patients prone to severe hypoglycaemia should be made aware of the elevated risk of subsequent cardiovascular events. [ABSTRACT FROM AUTHOR]

Aims: We aimed to estimate the use of healthcare services and the direct medical costs accrued by patients with diabetes mellitus (DM) during the year of the first severe hypoglycaemia (SH) event, as well as during the years before and after the event year. Materials and Methods: We analysed a population‐based, retrospective cohort including all adults with DM managed in the primary care setting from the Hong Kong Hospital Authority between 2006 and 2013. DM patients for whom SH was first recorded during the designated period were identified and matched to a control group of patients who had not experienced an SH event using the propensity score method. Direct medical costs in the years before, during and after the first SH event were determined by totalling the costs of health services utilized within respective years. Results: After matching, a total of 22 694 DM patients were divided into the first recorded‐SH group (n = 11 347) and the non‐SH control group (n = 11 347). Patients for whom SH was first recorded, on average, made 7.85 outpatient clinic visits, made 1.89 emergency visits and spent 17.75 nights hospitalized during the event year. Mean direct medical costs during the event year were 11 751 US$, more than 2‐fold that during the preceding year (4846 US$; P < 0.001) and subsequent years (4198–4700 US$; P < 0.001) and was 4.5 times that 2 years before the event (2481 US$; P < 0.001). Incremental costs of SH patients vs matched controls during the event year and the preceding year were 10 873 US$ (P < 0.001) and 3974 US$ (P < 0.001), respectively. Conclusions: SH is associated with excessive hospital admission rates and direct medical costs during the event year and, in particular, during the year before as compared to patients who had not experienced an SH event. [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]

Aim: To identify factors associated with documented symptomatic and severe hypoglycaemia over 4 years in people with type 2 diabetes starting insulin therapy. Materials and methods: CREDIT, a prospective international observational study, collected data over 4 years on people starting any insulin in 314 centres; 2729 and 2271 people had hypoglycaemia data during the last 6 months of years 1 and 4, respectively. Multivariable logistic regression was used to select the characteristics associated with documented symptomatic hypoglycaemia, and the model was tested against severe hypoglycaemia. Results: The proportions of participants reporting ≥1 non‐severe event were 18.5% and 16.6% in years 1 and 4; the corresponding proportions of those achieving a glycated haemoglobin (HbA1c) concentration <7.0% (<53 mmol/mol) were 24.6% and 18.3%, and 16.5% and 16.2% of those who did not. For severe hypoglycaemia, the proportions were 3.0% and 4.6% of people reaching target vs 1.5% and 1.1% of those not reaching target. Multivariable analysis showed that, for documented symptomatic hypoglycaemia at both years 1 and 4, baseline lower body mass index and more physical activity were predictors, and lower HbA1c was an explanatory variable in the respective year. Models for documented symptomatic hypoglycaemia predicted severe hypoglycaemia. Insulin regimen was a univariate explanatory variable, and was not retained in the multivariable analysis. Conclusions: Hypoglycaemia occurred at significant rates, but was stable over 4 years despite increased insulin doses. The association with insulin regimen and with oral agent use declined over that time. Associated predictors and explanatory variables for documented symptomatic hypoglycaemia conformed to clinical impressions and could be extended to severe hypoglycaemia. Better achieved HbA1c was associated with a higher risk of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Aim Hypoglycaemia and the fear of hypoglycaemia are barriers to achieving normoglycaemia with insulin. Insulin degludec ( IDeg) has an ultra-long and stable glucose-lowering effect, with low day-to-day variability. This pre-planned meta-analysis aimed to demonstrate the superiority of IDeg over insulin glargine ( IGlar) in terms of fewer hypoglycaemic episodes at equivalent HbA1c in type 2 and type 1 diabetes mellitus (T2DM/T1DM). Methods Pooled patient-level data for self-reported hypoglycaemia from all seven (five in T2DM and two in T1DM) randomized, controlled, phase 3a, treat-to-target trials in the IDeg clinical development programme comparing IDeg once-daily ( OD) vs. IGlar OD were analysed. Results Four thousand three hundred and thirty subjects (2899 IDeg OD vs. 1431 IGlar OD) were analysed. Among insulin-naïve T2DM subjects, significantly lower rates of overall confirmed, nocturnal confirmed and severe hypoglycaemic episodes were reported with IDeg vs. IGlar: estimated rate ratio ( RR):0.83[0.70;0.98]95% CI, RR:0.64[0.48;0.86]95% CI and RR:0.14[0.03;0.70]95% CI. In the overall T2DM population, significantly lower rates of overall confirmed and nocturnal confirmed episodes were reported with IDeg vs. IGlar [ RR:0.83[0.74;0.94]95% CI and RR:0.68[0.57;0.82]95% CI). In the T1DM population, the rate of nocturnal confirmed episodes was significantly lower with IDeg vs. IGlar during maintenance treatment ( RR:0.75[0.60;0.94]95% CI). Reduction in hypoglycaemia with IDeg vs. IGlar was more pronounced during maintenance treatment in all populations. Conclusions The limitations of this study include the open-label design and exclusion of subjects with recurrent severe hypoglycaemia. This meta-analysis confirms that similar improvements in HbA1c can be achieved with fewer hypoglycaemic episodes, particularly nocturnal episodes, with IDeg vs. IGlar across a broad spectrum of patients with diabetes. [ABSTRACT FROM AUTHOR]