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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: The HypoCOMPaSS multi‐centre trial achieved improvement in hypoglycaemia awareness and 20‐fold reduction in severe hypoglycaemia (SH) in a cohort with long‐standing type 1 diabetes (T1D). All participants received 'my hypo compass' (MHC) brief structured psycho‐educational intervention in addition to optimisation of insulin delivery/glucose monitoring. In this 24‐week, prospective, single‐centre feasibility RCT, we piloted MHC as a sole intervention in comparison to standard clinical care alone (CON). Methods: Participants with T1D and impaired hypoglycaemia awareness (IAH) (Clarke score ≥4) were recruited. MHC comprised a group/individual 1–2 h face‐to‐face session followed by a telephone call and second face‐to‐face session at 4 weeks. Outcome measures at 24 weeks were compared with baseline. Results: Fifty‐two individuals provided consent for screening with 39 fulfilling eligibility criteria. Fifteen withdrew before any study intervention. Twenty‐four adults with (mean ± SD) T1D duration 41.0 ± 15.1 years commenced/completed the study (100% visit attendance); 12 randomised to MHC and 12 to CON. All had IAH at baseline and at 24 weeks. Annualised SH rate following MHC was 3.8 ± 19.0 (24 weeks) versus 12.6 ± 3.5 (Baseline) and in CON group 2.0 ± 19.0 (24 weeks) versus 4.6 ± 11.5 (Baseline). 'Immediate Action' for and 'Worry' about hyperglycaemia measured by the Hyperglycaemia Avoidance Scale appeared lower following MHC. Participants attended all study visits and reflected positively on the MHC intervention. Conclusions: Feasibility of MHC implementation without additional intervention has been demonstrated. MHC education was associated with positive changes in attitudes and behaviours with the potential to reduce SH risk. MHC provides a validated, simple, well‐received programme to fulfil the educational component within RCTs targeting problematic hypoglycaemia and as part of holistic clinical care. [ABSTRACT FROM AUTHOR]

Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1β, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage. [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]

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]

Aims: Impaired awareness of hypoglycaemia (IAH) has been reported to affect up to a third of people with type 1 diabetes. Whether the increased use of sensor technology has changed its prevalence remains unknown. The aim of this study was to investigate the current prevalence of IAH and its change over time in a cohort of individuals with type 1 diabetes. Methods: IAH was assessed using the modified Clarke questionnaire in adults with type 1 diabetes. Participants were recruited from the diabetes outpatient clinic from February 2020 through April 2021. The scores were compared to similar data collected during previous assessments in 2006, 2010 and 2016 respectively. Results: A total of 488 individuals (51.2% male) with a mean (±SD) age of 51.3 ± 15.9 years, median [Q1–Q3] diabetes duration of 30 [16–40] years and mean HbA1c of 60 ± 12 mmol/mol (7.7 ± 1.1%) were included. Sensors were used by 85% of the study population. IAH was present among 78 (16.0%) participants, whereas 86 (17.6%) participants had a history of severe hypoglycaemia. By comparison, the prevalence of IAH equalled 32.5% in 2006, 32.3% in 2010 and 30.1% in 2016 (p for trend <0.001), while the proportion of individuals reporting severe hypoglycaemia equalled 21.2%, 46.7% and 49.8% respectively (p for trend 0.010). Comparing sequential assessments over time, the proportion of individuals with persistent IAH decreased from 74.0% and 63.6% between 2006 and 2016 to 32.5% in 2020. Conclusions: Among individuals with type 1 diabetes and high use of sensor technology, the current prevalence of IAH was 16%, about 50% lower as compared to previous years. [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]

Aims/hypothesis: Islet transplantation has been studied in small cohorts of recipients with type 1 diabetes complicated by severe hypoglycaemic events (SHEs). We determined factors associated with favourable outcomes in a large cohort of recipients reported to the Collaborative Islet Transplant Registry (CITR). Methods: In 398 non-uraemic islet transplant alone (ITA) recipients with type 1 diabetes and SHEs, transplanted between 1999 and 2015 and with at least 1 year follow-up, we analysed specified favourable outcomes against each of all available characteristics of pancreas donors, islet grafts, recipients and immunosuppressive regimens, as well as immunosuppression and procedure-related serious adverse events (SAEs). Results: Four factors were associated with the highest rates of favourable outcomes: recipient age ≥35 years; total infused islets ≥325,000 islet equivalents; induction immunosuppression with T cell depletion and/or TNF-α inhibition; and maintenance with both mechanistic target of rapamycin (mTOR) and calcineurin inhibitors. At 5 years after the last islet infusion, of the recipients meeting these four common favourable factors (4CFF; N=126), 95% were free of SHEs, 76% had HbA1c <53 mmol/mol (7.0%), 73% had HbA1c <53 mmol/mol (7.0%) and absence of SHEs, and 53% were insulin independent, significantly higher rates than in the remaining recipients (<4CFF; N=272). The incidence of procedural and immunosuppression-related SAEs per recipient that resulted in sequelae, disability or death was low in both the 4CFF (0.056 per person) and <4CFF (0.074 per person) groups. Conclusions/interpretation: In recipients with type 1 diabetes complicated by SHEs, islet transplantation meeting 4CFF protected 95% from SHEs at 5 years after the last islet infusion and exerted a large and significant benefit on glycaemic control, with an acceptable safety profile for this subgroup of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims To collect and analyse representative data of structural and process quality in the management of diabetic emergencies in Germany in 2020. Methods A standardised questionnaire comprising detailed items concerning clinically relevant parameters on the structural and process quality of out-of-hospital management of diabetic emergencies was sent nationwide to medical directors of emergency medical service districts (EMSDs). Results were compared with those from a similar study conducted in 2001. Results The return rate of the questionnaires represented 126 EMSDs, serving a total population of > 40.1 million. Only 4% of ambulances carried glucagon (6% in 2001). In 2020, blood glucose determination increased significantly to 71% of all emergency interventions and to 29% of suspected cardiac emergencies (24% and 15%, respectively, in 2001). In 100% of EMSDs severe hypoglycaemia (SH) was treated by paramedics by administering intravenous dextrose before the arrival of a doctor compared to 63% in 2001. The potential value of nasal glucagon was acknowledged by 43% of responders. In selected patients, treatment of SH was conducted without hospital admission in 78% of EMDs (60% in 2001). Fifty-three percent of medical directors acknowledged the need for further training in diabetic emergencies (47% in 2001). Cooperation for medical education between emergency teams and a diabetes centre was reported by 14% (41% in 2001). Conclusion Structural and process quality of the management of diabetic emergencies in Germany has improved considerably since 2001. Persisting deficiencies could be improved by providing better medical equipment in ambulances and ongoing education to the entire emergency teams. [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: To examine maternal fear of hypoglycaemia, glycaemia and pregnancy outcomes in women with impaired and normal awareness of hypoglycaemia. Methods: A pre‐planned sub‐study of 214 pregnant women with type 1 diabetes who participated in the CONCEPTT trial. Participants completed hypoglycaemia fear surveys (HFS‐II) at baseline. Logistic regression and Poisson regression analyses were used to obtain an adjusted estimate for the rate ratio relating awareness to the number of severe hypoglycaemic episodes, and for several neonatal outcomes in relation to the total HFS‐II score. The role of continuous glucose monitoring (CGM) use was examined. Results: Overall, 30% of participants reported impaired awareness of hypoglycaemia (n = 64). Women with impaired awareness of hypoglycaemia had more episodes of severe hypoglycaemia (mean 0.44 vs. 0.08, p < 0.001) (12–34 weeks gestation) and scored higher on the HFS‐II scale (43.7 vs. 36.0, p 0.008), indicating more fear of hypoglycaemia. They spent more time below range (CGM <3.5 mmol/L) and exhibited more glycaemic variability at 12 weeks gestation. Higher overall HFS‐II scores were associated with a higher risk of maternal severe hypoglycaemia episodes (Rate Ratio 1.78, 95% CI 1.39–2.27). Women with impaired awareness of hypoglycaemia had less maternal weight gain but there were no differences in neonatal outcomes between women with impaired awareness of hypoglycaemia and normal hypoglycaemia awareness. Higher HFS‐II scores were associated with more nephropathy (Odds Ratio 1.91, 95% CI 1.06–3.4). CGM use after 12 weeks was not associated with the number of episodes of severe hypoglycaemia (RR 0.75, 95% CI 0.49–1.15; p = 0.18). Conclusions: In pregnant women with type 1 diabetes, impaired awareness of hypoglycaemia is associated with more maternal severe hypoglycaemia episodes and more fear of hypoglycaemia. Having impaired awareness of hypoglycaemia and/or fear of hypoglycaemia should alert clinicians to this increased risk. Reassuringly, there was no increase in adverse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Objective: Prior to the Continuous Monitoring and Control of Hypoglycaemia (COACH) study described herein, no study had been powered to evaluate the impact of non‐adjunctive RT‐CGM use on the rate of debilitating moderate or severe hypoglycaemic events. Research Design and Methods: In this 12‐month observational study, adults with insulin‐requiring diabetes who were new to RT‐CGM participated in a 6‐month control phase where insulin dosing decisions were based on self monitoring of blood glucose values, followed by a 6‐month phase where decisions were based on RT‐CGM data (i.e. non‐adjunctive RT‐CGM use); recommendations for RT‐CGM use were made according to sites' usual care. The primary outcome was change in debilitating moderate (requiring second‐party assistance) and severe (resulting in seizures or loss of consciousness) hypoglycaemic event frequency. Secondary outcomes included changes in HbA1c and diabetic ketoacidosis (DKA) frequency. Results: A total of 519 participants with mean (SD) age 50.3 (16.1) years and baseline HbA1c 8.0% (1.4%) completed the study, of whom 32.8% had impaired hypoglycaemia awareness and 33.5% had type 2 diabetes (T2D). The mean (SE) per‐patient frequency of hypoglycaemic events decreased by 63% from 0.08 (0.016) during the SMBG phase to 0.03 (0.010) during the RT‐CGM phase (p = 0.005). HbA1c decreased during the RT‐CGM phase both for participants with type 1 diabetes (T1D) and T2D and there was a trend towards larger reductions among individuals with higher baseline HbA1c. Conclusions: Among adults with insulin‐requiring diabetes, non‐adjunctive use of RT‐CGM data is safe, resulting in significantly fewer debilitating hypoglycaemic events than management using SMBG. [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]

Abstract Background Severe hypoglycaemia carries a significant risk of morbidity and mortality for people with type 1 diabetes. Economic costs are also high, estimated at approximately £13 million annually in England, UK. Continuous glucose monitoring (CGM) has been shown to reduce hypoglycaemia and associated fear, improve overall glycaemia and quality of life, and is cost-effective. Despite effective pathways in place with high levels of resource utilization, it has been reported there are low levels of follow-up, therapy change and specialist intervention after severe hypoglycaemia. This study is designed to assess the impact of providing real-time CGM to people with type 1 diabetes, who have had a recent episode of severe hypoglycaemia (within 72 h), compared to standard care. Methods/design Fifty-five participants with type 1 diabetes and a recent episode of severe hypoglycaemia, who are CGM naïve, will be recruited to the study. Participants will be randomised to CGM or standard care. The primary outcome is percentage time spent in hypoglycaemia (

Abstract Background Hypoglycaemia, especially nocturnal, remains the main limiting factor of achieving good glycaemic control in type 1 diabetes. The effect of first generation long-acting insulin analogues in reducing nocturnal hypoglycaemia is well documented in patient with type 1 diabetes. The effect of the newer long-acting insulin degludec on risk of nocturnal hypoglycaemia remains undocumented in patients with type 1 diabetes and recurrent severe nocturnal hypoglycaemia. The HypoDeg trial is designed to investigate whether insulin degludec in comparison with insulin glargine U100 is superior in limiting the occurrence of nocturnal hypoglycaemia in patients with recurrent nocturnal severe hypoglycaemia. This paper reports the study design of the HypoDeg trial. Methods/design A Danish investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, two-year cross-over study investigating the effect of insulin degludec versus insulin glargine U100 on frequency of nocturnal hypoglycaemia in patients with type 1 diabetes and one or more episodes of nocturnal severe hypoglycaemia during the preceding two years as the major inclusion criteria. Patients are randomised (1:1) to basal therapy with insulin degludec or insulin glargine. Insulin aspart is used as bolus therapy in both treatment arms. Discussion In contrast to most other insulin studies the HypoDeg trial includes only patients at high risk of hypoglycaemia. The HypoDeg trial will compare treatment with insulin degludec to insulin glargine U100 in terms of risk of nocturnal hypoglycaemic episodes in patients with type 1 diabetes with the greatest potential to benefit from near-physiological insulin replacement therapy. www.clinicaltrials.gov: NCT02192450.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires life-long administration of insulin. Optimal management of T1DM entails a good knowledge and understanding of this condition both by the physician and the patient. Recent introduction of novel insulin preparations, technological advances in insulin delivery and glucose monitoring, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring and improved understanding of the detrimental effects of hypoglycaemia and hyperglycaemia offer new opportunities and perspectives in T1DM management. Evidence from clinical trials suggests an important role of structured patient education. Our efforts should be aimed at improved metabolic control with concomitant reduction of hypoglycaemia. Despite recent advances, these goals are not easy to achieve and can put significant pressure on people with T1DM. The approach of physicians should therefore be maximally supportive. In this review, we provide an overview of the recent advances in T1DM management focusing on novel insulin preparations, ways of insulin administration and glucose monitoring and the role of metformin or sodium-glucose co-transporter 2 inhibitors in T1DM management. We then discuss our current understanding of the effects of hypoglycaemia on human body and strategies aimed at mitigating the risks associated with hypoglycaemia.

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]

Beta cell replacement therapy is currently the only treatment method that allows restoration of physiological endogenous insulin secretion in the amounts corresponding to the current body requirements. Beta cell replacement options available for highly selected patients with brittle type 1 diabetes include solid-organ pancreas and islet transplantation. Beta cell replacement therapy may be offered to patients with both good kidney function and renal failure. In progressive renal failure, beta cell transplantation may be performed simultaneously with kidney transplantation or afterwards. Islet autotransplantation is offered to patients submitted to total pancreatectomy. In patients with brittle type 1 diabetes who continue to experience life threatening severe hypoglycaemia episodes despite optimized insulin therapy, beta cell replacement helps improve hypoglycaemia awareness, thus reducing the risk of severe hypoglycaemia episodes, facilitates blood glucose control with normalization of haemoglobin A1c (HbA1c) level, and reduces microvascular disease progression. In patients undergoing total pancreatectomy, infusion of the patient's own islets isolated from the removed pancreas prevents blood glucose level excursions and reduces the risk of surgically-induced diabetes. In this article, we review the current indications and contraindications to beta cell replacement, expected benefits, and possible complications of beta cell transplantation. [ABSTRACT FROM AUTHOR]

Beta cell replacement allows for adequate blood glucose control, reduced progression or even reversal of microvascular complications, and improves the quality of life. Simultaneous pancreas and kidney transplantation is the best therapeutic option for patients with type 1 diabetes and end-stage renal disease resulting from diabetic nephropathy. However, when pancreas transplantation is contraindicated or unavailable, pancreatic islet transplantation is an alternative minimally invasive procedure. We report a patient after earlier simultaneous kidney and pancreas transplantation with a failed pancreas graft, and no option for pancreas retransplantation. In this patient pancreatic islet transplantation was performed. The latter resulted in an improved blood glucose control, restoration of hypoglycaemia awareness, and improved quality of life with stable good function of the kidney allograft. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the risk of severe hypoglycaemia for patients with Type 1 diabetes (T1D) when exposed to insulin regimens including human insulin only or insulin analogues. Methods: A total of 19 896 patients with T1D were extracted from the Danish National Patient Register. Of these, 6379 T1D patients experiencing 1 of more severe hypoglycaemic episodes (total of 17 242 episodes) were matched 1:1 with T1D patients without severe hypoglycaemia. A logistic regression model with last insulin regimen used as exposure was constructed to analyse the effect on severe hypoglycaemia. Results: People on a basal–bolus regimen with insulin analogues had a reduced risk of severe hypoglycaemia of 39% (odds ratio: 0.61, 95% confidence interval: 0.54–0.68) compared to patients on a basal–bolus human insulin only regimen. Furthermore, patients on a premixed regimen containing an insulin analogue had a 58% (odds ratio: 0.42, 95% confidence interval: 0.36–0.49) reduced risk of severe hypoglycaemia compared to patients on premixed human insulin only. Conclusion: This study indicates that use of a basal–bolus insulin regimen with an insulin analogue is safer with respect to severe hypoglycaemia in patients with T1D than the use of a basal–bolus human insulin only regimen. [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]

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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/hypothesis: The aim of this work was to investigate clinical outcomes following severe hypoglycaemia requiring prehospital emergency medical services (EMS) management. Methods: We carried out a prospective, observational study of adults with diabetes attended by prehospital EMS for management of severe hypoglycaemia between April 2016 and July 2017. Information on precipitants, hospitalisation, length of hospital stay and recurrence was collected at 1 and 3 months following the episode of severe hypoglycaemia. Median and logistic regression models examined predictive factors. Results: Five hundred and five adults (61% male, median age 67 years) participated in the study. Fifty-two per cent had type 1 diabetes, 43% type 2 diabetes and 5% were unsure of their diabetes type. Following EMS management of the index episode of severe hypoglycaemia, 50.3% were transported to hospital. Of those transported, 41.3% were admitted to hospital for ongoing management (20.8% of all participants). The following factors predicted hospital admission: older age (OR 1.28 [95% CI 1.02, 1.60] per 10 years), greater number of comorbidities (OR 1.27 [95% CI 1.08, 1.48] per morbidity), moderate–severe injury accompanying the hypoglycaemia (OR 5.24 [95% CI 1.07, 25.8] compared with nil–mild injury) and unknown cause of hypoglycaemia (OR 2.21 [95% CI 1.24, 3.94] compared with known cause). The median (interquartile range) length of hospital stay was 4 (2–7) days. During follow-up, recurrent severe hypoglycaemia attended by prehospital EMS was experienced by 10.7% of participants. Predictive factors of recurrent severe hypoglycaemia in 3 months were decreased HbA1c (OR 1.97 [95% CI 1.27, 3.06] per 10 mmol/mol decrease) and a greater number of antecedent severe hypoglycaemia episodes (OR 1.12 [95% CI 1.03, 1.23] per episode). Conclusions/interpretation: Following an episode of severe hypoglycaemia managed by EMS, one-fifth of participants required hospital admission, more likely in those with advancing age, increasing comorbidities and injury and one-tenth required EMS again for severe hypoglycaemia in a 3 month period, more likely in those with a greater number of antecedent episodes and lower HbA1c. Knowledge of these factors associated with admission and recurrence provides an opportunity for development of targeted strategies aimed at prevention of severe hypoglycaemia in those most vulnerable. [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]

Introduction: In healthy carriers of the T allele of the transcription factor 7-like 2 (TCF7L2), fasting plasma glucagon concentrations are lower compared with those with the C allele. We hypothesised that presence of the T allele is associated with a diminished glucagon response during hypoglycaemia and a higher frequency of severe hypoglycaemia (SH) in type 1 diabetes (T1DM). Material and methods: This is a post hoc study of an earlier prospective observational study of SH and four mechanistic studies of physiological responses to hypoglycaemia. 269 patients with T1DM were followed in a one-year observational study. A log-linear negative binomial model was applied with events of SH as dependent variable and TCF7L2 alleles as explanatory variable. In four experimental studies including 65 people, TCF7L2 genotyping was done and plasma glucagon concentration during experimental hypoglycaemia was determined. Results: Incidences of SH were TT 0.54, TC 0.98 and CC 1.01 episodes per patient-year with no significant difference between groups. During experimental hypoglycaemia, the TCF7L2 polymorphism did not influence glucagon secretion. Discussion: Patients with T1DM carrying the T allele of the TCF7L2 polymorphism do not exhibit diminished glucagon response during hypoglycaemia and are not at increased risk of severe hypoglycaemia compared with carriers of the C allele.

Abstract Aim This study aimed to assess the association between body mass index (BMI) and the development of severe hypoglycaemia in patients with type 2 diabetes (T2D), using nationwide data for the entire South Korean population. Methods The association between BMI and severe hypoglycaemia was retrospectively examined from claims and National Health examination data registered between 2002 and 2015. A total of 1,366,692 subjects assigned clinical codes for T2D and prescribed antihypoglycaemic agents were included. The primary outcome was an episode of severe hypoglycaemia after the baseline health examination. Results A total of 37,682 subjects (2.7%) experienced a new severe hypoglycaemic event during the follow-up period (mean: 8.6 years). An inverse J-shaped association was observed between BMI and severe hypoglycaemic events. The association between low BMI and high risk of severe hypoglycaemia was similar in subjects who had never smoked, did not consume alcohol, did not use insulin and had no major comorbidities, after adjusting for multiple confounding variables. This association was also found to be intensified in men, young people aged 30–49 years, those with major comorbidities and insulin users. Conclusion BMI and severe hypoglycaemia were found to be inversely associated. Thus, those who fall into the category of having low BMI and high risk of severe hypoglycaemia should be warned about the risk of having a hypoglycaemic event and be properly informed about hypoglycaemia to minimize the risk of fatal hypoglycaemia-related outcomes. [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]

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]

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires life-long administration of insulin. Optimal management of T1DM entails a good knowledge and understanding of this condition both by the physician and the patient. Recent introduction of novel insulin preparations, technological advances in insulin delivery and glucose monitoring, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring and improved understanding of the detrimental effects of hypoglycaemia and hyperglycaemia offer new opportunities and perspectives in T1DM management. Evidence from clinical trials suggests an important role of structured patient education. Our efforts should be aimed at improved metabolic control with concomitant reduction of hypoglycaemia. Despite recent advances, these goals are not easy to achieve and can put significant pressure on people with T1DM. The approach of physicians should therefore be maximally supportive. In this review, we provide an overview of the recent advances in T1DM management focusing on novel insulin preparations, ways of insulin administration and glucose monitoring and the role of metformin or sodium-glucose co-transporter 2 inhibitors in T1DM management. We then discuss our current understanding of the effects of hypoglycaemia on human body and strategies aimed at mitigating the risks associated with hypoglycaemia. [ABSTRACT FROM AUTHOR]