Clinical and socio‐demographic factors associated with diabetic ketoacidosis hospitalization in adults with Type 1 diabetes

Aim

To identify the clinical and socio‐demographic factors associated with hospitalization for diabetic ketoacidosis in adults with Type 1 diabetes.

Methods

We combined clinical and administrative health data from a large urban diabetes clinic to perform a data linkage study. We identified adults (aged ≥ 18 years old) with Type 1 diabetes and linked to hospital discharge abstracts to assess for diabetic ketoacidosis hospitalization. The study period was between 1 January 2004 and 31 December 2009, with all individuals living in the same geographic area. Multivariate logistic regression was used to identify potential predictors of diabetic ketoacidosis hospitalization.

Results

We identified 255 individuals with a diabetic ketoacidosis hospitalization and 1739 without a diabetic ketoacidosis hospitalization. Mean (standard deviation) age was 40.0 (15.8) years, 51.7% were men and mean duration of diabetes was 17.8 (12.9) years. Diabetic ketoacidosis hospitalization was associated with shorter duration of diabetes (odds ratio 0.96 per year; 95% confidence interval 0.95–0.98), gastroparesis (odds ratio 4.13; 95% confidence interval 1.82–9.35), psychiatric diagnosis (odds ratio 1.98; 95% confidence interval 1.22–3.19), and higher HbA_1c (odds ratio 1.25 per 1% increase; 95% confidence interval 1.16–1.35).

Conclusions

This study identifies specific clinical factors associated with diabetic ketoacidosis hospitalization in adults with Type 1 diabetes. This information can help to inform the detection of high‐risk patients, for whom special attention and interventions may be warranted to prevent diabetic ketoacidosis.     

Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1‐year patient‐level meta‐analysis of the EDITION clinical studies in people with type 2 diabetes

Aims

To investigate the efficacy and safety of insulin glargine 300 U/mL (Gla‐300) vs insulin glargine 100 U/mL (Gla‐100) over 12 months in a patient‐level meta‐analysis, using data from the EDITION studies in people with type 2 diabetes (T2DM).

Methods

EDITION 1, 2 and 3 were multicentre, randomized, open‐label, 2‐arm, parallel‐group, treat‐to‐target phase IIIa studies. Similar study designs and endpoints enabled a meta‐analysis to be conducted.

Results

Reductions in glycated haemoglobin (HbA1c) were better sustained over 12 months with Gla‐300 than with Gla‐100 (least squares [LS] mean difference in change from baseline: ?0.10 % [95% confidence interval {CI} ?0.18 to ?0.02] or ?1.09 mmol/mol [95% CI ?2.01 to ?0.20]; P = .0174). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycaemia was 15% lower with Gla‐300 vs Gla‐100 at night (relative risk 0.85 [95% CI 0.77–0.92]) and 6% lower at any time of day (relative risk 0.94 [95% CI 0.90–0.98]). Rates of hypoglycaemia were 18% lower with Gla‐300 vs Gla‐100 at night (rate ratio 0.82 [95% CI 0.67–0.99]), but comparable at any time of day. HbA1c <7.0 % without nocturnal hypoglycaemia was achieved by 24% more participants with Gla‐300 than with Gla‐100 (relative risk 1.24 [95% CI 1.03–1.50]). Severe hypoglycaemia was rare; in both treatment groups the incidence of events at any time of day was ≤3.6%, while rates were ≤0.08 events per participant‐year.

Conclusions

In a broad population of people with T2DM over 12 months, use of Gla‐300 provided more sustained glycaemic control and significantly lower hypoglycaemia risk at night and at any time of day compared with Gla‐100.     

A retrospective observational study of people with Type 1 diabetes with self‐reported severe hypoglycaemia reveals high level of ambulance attendance but low levels of therapy change and specialist intervention

Aim

To evaluate the impact of severe hypoglycaemia on NHS resources and overall glycaemic control in adults with Type 1 diabetes.

Methods

An observational, retrospective study of adults (aged ≥ 18 years) with Type 1 diabetes reporting one or more episodes of severe hypoglycaemia during the preceding 24 months in 10 NHS hospital diabetes centres in England and Wales. The primary outcome was healthcare resource utilization associated with severe hypoglycaemia. Secondary outcomes included demographic and clinical characteristics, diabetes control and pathway of care.

Results

Some 140 episodes of severe hypoglycaemia were reported by 85 people during the 2‐year observation period. Ambulances were called in 99 of 140 (71%) episodes and Accident and Emergency attendance occurred in 26 of 140 (19%) episodes, whereas 29 of 140 (21%) episode required no immediate help from healthcare providers. Participants attended a median of 5 (range 0–58) diabetes clinic consultations during the observation period; 13% (70 of 552) of all consultations were severe hypoglycaemia‐related. Of the HbA_1c measurements recorded closest prior to severe hypoglycaemia (n = 119), only 7 of 119 measurements were < 48 mmol/mol (< 6.5%) and mean HbA_1c was 70 (sd 19) mmol/mol (8.5%, sd 1.7%). Some 119 changes to diabetes treatment were recorded during the observation period (median/person 0;, range 0–11), of which 52 of 119 changes (44%) followed severe hypoglycaemic events.

Conclusions

We observed a high level of ambulance service intervention but surprisingly low levels of hypoglycaemia follow‐up, therapy change and specialist intervention in people self‐reporting severe hypoglycaemia. These results suggest there may be important gaps in care pathways for people with Type 1 diabetes self‐reporting severe hypoglycaemia.     

Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4‐week,double‐blind,randomized, placebo‐controlled phase 2 trial

Aims

This phase 2, double‐blind, randomized, placebo‐controlled trial ( ClinicalTrials.gov NCT02702011) with 4 sites in Japan investigated the pharmacodynamics (PD), pharmacokinetics (PK) and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin.

Materials and methods

Participants using multiple daily injections of insulin for ≥12 months, with HbA1c of 7.5%‐10.0%, entered a 2‐week, open‐label, placebo run‐in period, followed by a 4‐week, double‐blind period during which participants were randomized 1:1:1:1 to receive empagliflozin 2.5 mg (n = 13), empagliflozin 10 mg (n = 12), empagliflozin 25 mg (n = 12) or placebo (n = 11). The primary objective was to assess the effect of empagliflozin vs placebo on urinary glucose excretion (UGE) after 7 days of treatment.

Results

PD: Empagliflozin resulted in a dose‐dependent significant increase in 24‐hour UGE compared with placebo (UGE placebo‐corrected mean [95% confidence interval] change from baseline: 2.5 mg, 65.10 [43.29, 86.90] g/24 h; 10 mg, 81.19 [58.80, 103.58] g/24 h; 25 mg, 98.11 [75.91, 120.31] g/24 h). After 4 weeks of treatment, UGE increase was associated with improved glycaemic control, reduced body weight and decreased insulin needs. Empagliflozin treatment also resulted in dose‐dependent increases in serum ketone bodies and free fatty acids. PK: Plasma empagliflozin levels increased in a dose‐dependent manner and peaked at 1.5 hours. In this short study, empagliflozin was well tolerated, with no increase in rate of hypoglycaemia and no diabetic ketoacidosis events reported.

Conclusions

Based on this short‐duration phase 2 study, the PK/PD profile of empagliflozin in Japanese participants with T1DM is comparable to that of non‐Japanese participants.     

Comparing hormonal and symptomatic responses to experimental hypoglycaemia in insulin‐ and sulphonylurea‐treated Type 2 diabetes

Aims Patients with diabetes rely on symptoms to identify hypoglycaemia. Previous data suggest patients with Type 2 diabetes develop greater symptomatic and hormonal responses to hypoglycaemia at higher glucose concentrations than non‐diabetic controls and these responses are lowered by insulin treatment. It is unclear if this is as a result of insulin therapy itself or improved glucose control. We compared physiological responses to hypoglycaemia in patients with Type 2 diabetes patients treated with sulphonylureas (SUs) or insulin (INS) with non‐diabetic controls (CON). Methods Stepped hyperinsulinaemic hypoglycaemic clamps were performed on 20 subjects with Type 2 diabetes, 10 SU‐treated and 10 treated with twice‐daily premixed insulin, and 10 age‐ and weight‐matched non‐diabetic controls. Diabetic subjects were matched for diabetes duration, glycated haemoglobin (HbA_1c) and hypoglycaemia experience. We measured symptoms, counterregulatory hormones and cognitive function at glucose plateaux of 5, 4, 3.5, 3 and 2.5 mmol/l. Results Symptomatic responses to hypoglycaemia occurred at higher blood glucose concentrations in SU‐treated than INS‐treated patients [3.5 (0.4) vs. 2.6 (0.5) mmol/l SU vs. INS; P = 0.001] or controls [SU vs. CON 3.5 (0.4) vs. 3.0 (0.6) mmol/l; P = 0.05]. They also had a greater increase in symptom scores at hypoglycaemia [13.6 (11.3) vs. 3.6 (6.1) vs. 5.1 (4.3) SU vs. INS vs. CON; P = 0.017]. There were no significant differences in counterregulatory hormone responses or impairment of cognitive function among groups. Conclusions Sulphonylurea‐treated subjects are more symptomatic of hypoglycaemia at a higher glucose level than insulin‐treated subjects. This may protect them from severe hypoglycaemia but hinder attainment of glycaemic goals.     

Sodium‐glucose co‐transporter‐2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: A randomized,open‐label, 3‐arm parallel comparative,exploratory study

This study investigated the safety and efficacy of the sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor luseogliflozin with differing carbohydrate intakes in Japanese individuals with type 2 diabetes (T2D). Participants were randomly assigned to 3 carbohydrate‐adjusted meals for 14 days (days 1‐14; a high carbohydrate [HC; 55% total energy carbohydrate] and high glycaemic index [HGI] meal; an HC [55% total energy carbohydrate] and low glycaemic index [LGI] meal; or a low carbohydrate [LC; 40% total energy carbohydrate] and HGI meal). All participants received luseogliflozin for the last 7 days (days 8‐14), continuous glucose monitoring (CGM) before and after luseogliflozin treatment (days 5‐8 and days 12‐15) and blood tests on days 1, 8 and 15. Luseogliflozin significantly decreased the area under the curve and mean of CGM values in all 3 groups similarly. Fasting plasma glucose, insulin and glucagon were similar at all time points. Ketone bodies on day 15 were significantly higher in the LC‐HGI group compared with the HC‐HGI and HC‐LGI groups. In conclusion, luseogliflozin has similar efficacy and safety in Japanese people with T2D when meals contain 40% to 55% total energy carbohydrate, but a strict LC diet on this class of drug should be avoided to prevent SGLT2 inhibitor‐associated diabetic ketoacidosis.     

Education is the strongest socio‐economic predictor of smoking in pregnancy

Aims

To investigate socio‐economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions.

Design

Cross‐sectional analysis with linked survey and register data.

Setting

South‐western Finland.

Participants

A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study.

Measurements

The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire‐based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio‐economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated.

Findings

Mother's education was the strongest socio‐economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2–3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1–9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95% CI = 1.4–6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0–18.2; P < 0.001) for vocational secondary education and 14.4 (95% CI = 6.3–33.0; P < 0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1–3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4–2.8; P < 0.001), but did not attenuate its socio‐economic disparities.

Conclusions

In Finland, socio‐economic disparities in smoking in pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general).     

Comparison of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) in paediatric Type 1 diabetes: a multicentre matched‐pair cohort analysis over 3 years

Aims To conduct a multicentre, matched‐pair cohort analysis comparing glycaemic control and adverse events of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) in paediatric patients. Methods Using standardized computer‐based prospective documentation, HbA_1c, insulin dose, body mass index–standard deviation score (BMI–SDS), rate of hypoglycaemia, rate of diabetic ketoacidosis (DKA) and intensity of care were analysed in 434 matched pairs during a follow‐up period of 3 years after initiation of MDI or CSII. Results HbA_1c was significantly lower in the CSII group during the first year of new regimen (CSII 7.5 ± 0.05 vs. MDI 7.7 ± 0.06; P < 0.05), but rose to the same level as in the MDI group during year 3. Insulin requirement remained significantly lower in the CSII group. The BMI–SDS increased in both study groups, with no significant difference. The rate of severe hypoglycaemia decreased significantly after the change of regimen (CSII 17.87 ± 2.85 vs. MDI 25.14 ± 3.79; P < 0.05) and during year 3 of the regimen, particularly when compared with baseline (?21% vs. ?16%). The rate of DKA was lower at baseline in the CSII group and remained significantly lower over all 3 years. Intensity of care was the same in both subsets. Conclusions Employing a large cohort, this matched‐pair analysis has demonstrated over a 3‐year study period that CSII is a safe form of intensive insulin therapy with similar glycaemic effects, but with significantly reduced rates of hypoglycaemia and DKA and a lower insulin requirement when compared with MDI.     

Clinical outcomes in real‐world patients with type 2 diabetes switching from first‐ to second‐generation basal insulin analogues: Comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort study

Aims

To compare clinical outcomes in patients with type 2 diabetes (T2D) switching from insulin glargine 100 units/mL (Gla‐100) or insulin detemir (IDet) to insulin glargine 300 units/mL (Gla‐300) or insulin degludec (IDeg).

Materials and Methods

We conducted a retrospective, observational study of electronic medical records for Gla‐300/IDeg adult switchers (March 1, 2015 to January 31, 2017) with active records for 12‐month baseline (glycated haemoglobin [HbA1c] used a 6‐month baseline period) and 6‐month follow‐up periods. Gla‐300 and IDeg switchers were propensity score‐matched using baseline demographic and clinical characteristics. Outcomes were HbA1c change and goal attainment (among patients with HbA1c captured at follow‐up), and hypoglycaemia with fixed follow‐up (intention‐to‐treat [ITT]; 6 months) and variable follow‐up (on‐treatment [OT]; to discontinuation or 6 months).

Results

Each matched cohort comprised 1592 patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and <8.0% [64 mmol/mol]) attainment rates were similar for Gla‐300 (n = 742) and IDeg (n = 727) switchers. Using fixed follow‐up (ITT method), hypoglycaemia incidence decreased significantly from baseline with Gla‐300 (all hypoglycaemia: 15.6% to 12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department [ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and event rate were found at follow‐up (ITT) for Gla‐300 vs IDeg. Using variable follow‐up (OT), hypoglycaemia incidence was similar in both groups, but Gla‐300 switchers had a lower inpatient/ED hypoglycaemia event rate at follow‐up (adjusted rate ratio 0.56; P = .016).

Conclusions

In a real‐world setting, switching from Gla‐100 or IDet to Gla‐300 or IDeg was associated with similar improvements in glycaemic control and hypoglycaemia in adult patients with T2D.     

Treat‐to‐target trials: uses,interpretation and review of concepts

Treat‐to‐target trial designs compare investigational insulins with a standard insulin. Treat‐to‐target trials force‐titrate insulin dosages to achieve a prespecified treatment goal. With comparable glycaemic control, comparisons of safety endpoints such as hypoglycaemia can be made to establish the risk‐benefit profile of the new insulin. Glargine versus NPH showed comparable A1C reductions; however, A1C <7% without associated nocturnal hypoglycaemia was reached in more patients on glargine and overall hypoglycaemia was lower. Detemir versus glargine showed non‐inferiority between the groups; however, with less weight gain and more injection site reactions with detemir. Detemir/aspart versus glargine/aspart showed non‐inferiority between the treatments, however, with less weight gain in the detemir group but comparable risk of hypoglycaemia. Degludec in combination with aspart versus glargine/aspart showed comparable A1C reductions. However, degludec‐treated patients had less overall hypoglycaemia and less nocturnal hypoglycaemia. Because insulin titrations are guided by goal attainment with each treatment, treat‐to‐target trials enable clinicians to determine differences in non‐glycaemic treatment effects, such as rates of hypoglycaemia and weight gain, at the same level of glycaemic control.     

Sotagliflozin: a dual sodium‐glucose co‐transporter‐1 and ‐2 inhibitor for the management of Type 1 and Type 2 diabetes mellitus

Aims

To evaluate the evidence for the novel dual sodium‐glucose co‐transporter‐1 (SGLT1) and ‐2 (SGLT2) inhibitor, sotagliflozin, which may enhance the efficacy of SGLT2 inhibitors by additionally reducing intestinal glucose absorption.

Methods

The search terms ‘sotagliflozin’, ‘LX4211’, ‘SGLT’ and ‘diabetes’ were entered into PubMed. Evidence for the pharmacokinetics, pharmacodynamics, safety and efficacy of sotagliflozin in Type 1 and 2 diabetes was extracted from the retrieved literature, critically evaluated, and contextualized in relation to data on existing SGLT2 inhibitors.

Results

There is convincing evidence from a range of phase II and III clinical trials that sotagliflozin significantly improves glycaemic control in both Type 1 and Type 2 diabetes. Additional benefits, such as smaller postprandial plasma glucose excursions, lower insulin requirements, appetite suppression and weight loss have been documented. While this is encouraging, several safety concerns remain; a dose‐dependent increase in the rate of diabetic ketoacidosis, diarrhoea and genital mycotic infection is apparent, although statistical exploration of the data regarding such events is currently lacking. Speculatively, use of a 200‐mg rather than a 400‐mg dose may help to limit unwanted effects.

Conclusions

The current evidence for sotagliflozin in diabetes appears promising. Further studies sufficiently powered to assess present and emerging safety concerns, as well as to identify individuals for whom sotagliflozin may be of particular benefit/harm would now be informative for regulatory decision‐making. Direct comparisons with existing SGLT2 inhibitors are also needed to determine relative safety/efficacy profiles for the different indications.

     

Socio‐economic status and HbA1c in type 2 diabetes: A systematic review and meta‐analysis

Up until now, differences in HbA_1c levels by socio‐economic status (SES) have been identified, but not yet quantified in people with type 2 diabetes. The aim of this study was therefore to assess the difference in HbA_1c levels between people with type 2 diabetes of different SES in a systematic review and meta‐analysis. A systematic literature search was conducted in MEDLINE, Embase, Ebsco, and the Cochrane Library until January 14, 2018. Included studies described adults with type 2 diabetes in whom the association between SES and HbA_1c levels was studied. Studies were rated for methodological quality and data were synthesized quantitatively (meta‐analysis) and qualitatively (levels of evidence), stratified for type of SES variable, i.e., education, income, deprivation, and employment. Fifty‐one studies were included: 15 high, 27 moderate, and 9 of low methodological quality. Strong evidence was provided that people of low SES have higher HbA_1c levels than people of high SES, for deprivation, education, and employment status. The pooled mean difference in HbA_1c levels between people of low and high SES was 0.26% (95% CI, 0.09‐0.43) or 3.12 mmol/mol (95% CI, 1.21‐5.04) for education and 0.20% (95% CI, ?0.05 to 0.46) or 2.36 mmol/mol (95%CI, ?0.61 to 5.33) for income. In conclusion, our systematic review and meta‐analysis showed that there was an inverse association between SES and HbA_1c levels in people with type 2 diabetes. Future research should focus on finding SES‐sensitive strategies to reduce HbA_1c levels in people with type 2 diabetes.     

Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease‐Modifying Antirheumatic Drugs: A Systematic Review and Meta‐Analysis

Objective

To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease‐modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis.

Methods

We conducted a systematic review and meta‐analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non‐TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle‐Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman‐Tukey‐type arcsine square root transformation, using a random‐effects model.

Results

Twenty‐five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8–2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5–2.6]), non‐TNF biologics (6.1% [95% CI 0.0–16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2–4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1–15.5]) than in those who did not (14.6% [95% CI 4.3–29.0]).

Conclusion

We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.

     

Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case–control study

Aims/hypothesis

We determined the impact of insulin pump therapy on long-term glycaemic control, BMI, rate of severe hypoglycaemia and diabetic ketoacidosis (DKA) in children.

Methods

Patients on pump therapy at a single paediatric tertiary hospital were matched to patients treated by injections on the basis of age, duration of diabetes and HbA_1c at the time of pump start. HbA_1c, anthropometric data, episodes of severe hypoglycaemia and rates of hospitalisation for DKA were collected prospectively.

Results

A total of 345 patients on pump therapy were matched to controls on injections. The mean age, duration of diabetes at pump start and length of follow-up were 11.4 (±?3.5), 4.1 (±?3.0) and 3.5 (±?2.5) years, respectively. The mean HbA_1c reduction in the pump cohort was 0.6% (6.6 mmol/mol). This improved HbA_1c remained significant throughout the 7 years of follow-up. Pump therapy reduced severe hypoglycaemia from 14.7 to 7.2 events per 100 patient-years (p?<?0.001). In contrast, severe hypoglycaemia increased in the non-pump cohort over the same period from 6.8 to 10.2 events per 100 patient-years. The rate of hospitalisation for DKA was lower in the pump cohort (2.3 vs 4.7 per 100 patient-years, p?=?0.003) over the 1,160 patient-years of follow-up.

Conclusions/interpretation

This is the longest and largest study of insulin pump use in children and demonstrates that pump therapy provides a sustained improvement in glycaemic control, and reductions of severe hypoglycaemia and hospitalisation for DKA compared with a matched cohort using injections.     

Psychosocial Predictors of Acute Complications of Diabetes in Youth

In this paper we determine whether individual and family psychosocial functioning predicts the risk for recurrent acute diabetic complications. An onset-cohort of 61 children and adolescents with Type 1 diabetes received conventional diabetes care. Episodes of ketoacidosis and of severe hypoglycemia were recorded for 8 years, and glycaemic control was measured by glycohaemoglobin. Measures of psychosocial functioning of the patient and parents were obtained during the first year. Over 8 years, 28% of subjects had at least one episode of ketoacidosis, and 21% had at least one episode of hypoglycaemia. The odds of observing recurrent hypoglycaemia versus recurrent ketoacidosis was 14 times greater in boys than in girls (Fisher's exact test p<0.05). Girls with recurrent ketoacidosis had more behaviour problems and lower social competence, they reported higher levels of family conflict, and their parents reported lower levels of family cohesion, expressiveness and organization in year one. These relationships were independent of any association with poor glycaemic control. Recurrent hypoglycaemia in boys was generally unrelated to individual and family functioning or glycohaemoglobin. Despite our small sample size, our findings are suggestive of relationships that may lead to early identification of patients who are prone to recurrent ketoacidosis, and to the development of early intervention strategies.     

Running on mixed fuel‐dual agonistic approach of GLP‐1 and GCG receptors leads to beneficial impact on body weight and blood glucose control: A comparative study between mice and non‐human primates

Aim

We performed acute and chronic studies in healthy and diet‐induced obese animals using mouse‐specific or monkey‐specific dual GLP‐1R/GCGR agonists to investigate their effects on food intake, body weight, blood glucose control and insulin secretion. The selective GLP‐1R agonist liraglutide was used as comparator.

Methods

The mouse‐specific dual agonist and liraglutide were tested in lean wild type, GLP‐1R knockout and diet‐induced obese mice at different doses. A chronic study was performed in DIO mice to investigate the effect on body weight, food consumption and total energy expenditure (TEE) in obese and diabetic monkeys with a focus on body weight and energy intake.

Results

The mouse‐specific dual agonist and liraglutide similarly affected glycaemic control. A higher loss in body weight was measured in dual agonist‐treated obese mice. The dual agonist significantly enhanced plasma glucose excursion in overnight fed GLP‐1R^?/? mice, probably reflecting a potent GCGR agonist activity. It increased TEE and enhanced fat and carbohydrate oxidation, while liraglutide produced no effect on TEE. In obese and diabetic monkeys, treatment with the monkey‐specific dual agonist reduced total energy intake to 60%‐70% of baseline TEI during chronic treatment. A decrease in body weight and significant improvement in glucose tolerance was observed.

Conclusions

In DIO mice and non‐human primates, dual agonists elicited robust glycaemic control, similar to the marketed GLP‐1R agonist, while eliciting greater effects on body weight. Results from DIO mice suggest that the increase in TEE is caused not only by increased fat oxidation but also by an increase in carbohydrate oxidation.     

The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): A short‐term cost‐effectiveness analysis in the UK setting

Aim

To evaluate the cost‐effectiveness of IDegLira versus basal‐bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK.

Methods

A Microsoft Excel model was used to evaluate the cost‐utility of IDegLira versus BBT over a 1‐year time horizon. Clinical input data were taken from the treat‐to‐target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event‐related disutilities were taken from published sources. Extensive sensitivity analyses were performed.

Results

IDegLira was associated with an improvement of 0.05 quality‐adjusted life years (QALYs) versus BBT, due to reductions in non‐severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost‐effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses.

Conclusions

IDegLira is a cost‐effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK.     

Psychosocial variables and presence,severity and prognosis of plantar heel pain: A systematic review of cross‐sectional and prognostic associations

Objective

Plantar heel pain (PHP) is often disabling, and persistent symptoms are common. Psychosocial variables are known to affect pain and disability but the association of these factors with PHP has yet to be established. The purpose of the present systematic review was to determine if psychosocial variables are associated with the presence, severity and prognosis of PHP.

Methods

A systematic review of the literature and qualitative synthesis was carried out. Electronic searches of MEDLINE, CINAHL, SPORTDiscus, PsycINFO and EMBASE were undertaken from the inception of the respective databases up to November 2017. Any study design incorporating measurements of psychosocial variables with participants with plantar heel pain were included. The quality of included articles was appraised using the Newcastle Ottawa Scale.

Results

Five articles from four studies were included in the review, with a total of 422 participants. Moderate‐level evidence suggested a clinically unimportant association with the incidence of PHP and depression, anxiety and stress, and limited evidence suggested a clinically unimportant association with job dissatisfaction. Moderate‐level evidence suggested that there may also be an association between depression, anxiety, stress and catastrophization and PHP pain, and between depression, anxiety, stress, catastrophization and kinesiophobia and PHP function. We also found moderate‐level evidence that a psychological disorder may be associated with a poorer outcome to shockwave therapy.

Conclusion

In light of this review, the association of psychosocial variables and plantar heel pain cannot be ruled out. Given recommendations to adopt an individualized and stratified approach to other musculoskeletal conditions, clinicians should remain vigilant to their presence.     

Association of hypoglycaemia severity with clinical,patient‐reported and economic outcomes in US patients with type 2 diabetes using basal insulin

Aims

To evaluate the clinical and patient‐reported outcomes and healthcare utilization and costs associated with patient‐reported hypoglycaemia in US adults with type 2 diabetes (T2D) treated with basal insulin.

Materials and methods

This was an observational, cross‐sectional, survey‐based study of adults with T2D on basal insulin ± oral antidiabetes drugs (OADs) or rapid‐acting/premixed insulin, who had in the past ever experienced hypoglycaemia, using US data from the National Health and Wellness Survey. Eligible patients were categorized as having no hypoglycaemia (38.7%), non‐severe hypoglycaemia (55.1%), or severe hypoglycaemia (6.2%) in the preceding 3 months. Outcomes included health‐related quality of life (HRQoL), work productivity and activity impairment, healthcare resource utilization, and estimated direct and indirect costs. Multivariable regression models were performed to control for patient characteristics.

Results

Patients who experienced severe hypoglycaemia had significantly (P < .05) lower HRQoL scores, greater overall impairment of work productivity and activity, greater healthcare resource utilization, and higher costs compared with those who experienced non‐severe or no hypoglycaemia. Patients with non‐severe hypoglycaemia also reported an impact on the number of provider visits, indirect costs, and HRQoL.

Conclusions

Patients with T2D using basal insulin ± OADs or rapid‐acting/premixed insulin in the United States who experienced severe hypoglycaemia had greater impairment of activity and work productivity, utilized more healthcare resources, and incurred higher associated costs than those with non‐severe or no hypoglycaemia. The study also demonstrated the impact that non‐severe hypoglycaemic events have on economic and HRQoL outcomes. Reducing the incidence and severity of hypoglycaemia could lead to clinically meaningful improvements in HRQoL and may result in lower healthcare utilization and associated costs.