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.     

Diabetic ketoacidosis at diagnosis in Austrian children in 1989–2008: a population-based analysis

Aim  

The aim of the study was to analyse the prevalence of diabetic onset ketoacidosis (DKA) during a period of 20 years (1989–2008) on a population basis in the whole of Austria.     

Early predictors of diabetic retinopathy in type 1 diabetes: The Retinopathy Champagne Ardenne Diabète (ReCAD) study

Aims

To determine the relationship between early markers of diabetes control and diabetic retinopathy (DR) in type 1 diabetes.

Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report

Background  

Mucormycosis (or zygomycosis) is the term for infection caused by fungi of the order Mucorales. Mucoraceae may produce severe disease in susceptible individuals, notably patients with diabetes and leukemia. Rhinocerebral mucormycosis most commonly manifests itself in the setting of poorly controlled diabetes, especially with ketoacidosis.     

Insulin pump use in pregnancy is associated with lower HbA1c without increasing the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1 diabetes

Aims/hypothesis

The aim of this study was to compare glycaemic control and maternal–fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI).

Methods

In a retrospective study, glycaemic control and outcomes of 387 consecutive pregnancies in women with type 1 diabetes who attended specialised clinics at three centres 2006–2010 were assessed.

Results

Women using insulin pumps (129/387) were older and had a longer duration of diabetes, more retinopathy, smoked less in pregnancy, and had more preconception care (p?<?0.01 for each). Among 113 pregnancies >20 weeks’ gestation in women on insulin pumps and 218 in women on MDI, there was a significant difference in HbA_1c in the first trimester (mean HbA_1c 6.90?±?0.71% (52?±?7.8 mmol/mol) vs 7.60?±?1.38% (60?±?15.1 mmol/mol), p?<?0.001), which persisted until the third trimester (mean HbA_1c 6.49?±?0.52% (47?±?5.7 mmol/mol) vs 6.81?±?0.85% (51?±?9.3 mmol/mol), p?=?0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs MDI (1.8% vs 3.0%, p?=?0.72). Despite lower HbA_1c, women on insulin pumps did not have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p?=?0.90) or more weight gain (16.3?±?8.7 vs 15.2?±?6.2 kg, p?=?0.18). More large-for-gestational-age infants in the pump group (55.0% vs 39.2%, p?=?0.007) may have resulted from confounding by parity.

Conclusions/interpretation

In this large multicentre study, women using insulin pumps in pregnancy had lower HbA_1c without increased risk of severe hypoglycaemia or diabetic ketoacidosis but no improvement in other pregnancy outcomes. This information can help inform care providers and patients about the glycaemic effectiveness and safety of insulin pumps in pregnancy.     

Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels

Aims/hypothesis

We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes.

Methods

The study is based on data from DanDiabKids, a Danish national diabetes register for children. The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996–2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods.

Results

The study population comprised 2,964 children <18 years. The prevalence of DKA at diagnosis was 17.9%. Of the total subjects, 8.3% had mild, 7.9% had moderate and 1.7% had severe DKA. DKA (moderate and severe) was associated with increased HbA_1c (%) levels (0.24; 95% CI 0.11, 0.36; p?=?0.0003) and increased insulin dose-adjusted HbA_1c (IDAA_1c, 0.51; 95% CI 0.31, 0.70; p?<?0.0001) during follow-up, after adjustment for covariates. Children without a family history of diabetes were more likely to present with DKA (19.2% vs 8.8%, p?<?0.0001); however, these children had a lower HbA_1c (%) level over time (?0.35; 95% CI ?0.46, ?0.24; p?<?0.0001). Continuous subcutaneous insulin infusion (CSII) was associated with a long-term reduction in HbA_1c, changing the effect of DKA, after adjustment for covariates (p?<?0.0001).

Conclusions/interpretation

DKA at diagnosis was associated with poor long-term metabolic regulation and residual beta cell function as assessed by HbA_1c and IDAA_1c, respectively; however, CSII treatment was associated with improvement in glycaemic regulation and residual beta cell function, changing the effect of DKA at onset in our population.     

HbA<Subscript>1c</Subscript> levels in schoolchildren with type 1 diabetes are seasonally variable and dependent on weather conditions

Aims/hypothesis  

We evaluated seasonal HbA_1c changes in children with type 1 diabetes and its relation with measures of weather conditions.     

Assessing the economic value of maintained improvements in Type 1 diabetes management,in terms of HbA1c,weight and hypoglycaemic event incidence

Aims

Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment‐related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed the health economic value of maintained reductions in HbA_1c, BMI and hypoglycaemia incidence among the UK Type 1 diabetes population.

Methods

The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life‐years and quality‐adjusted life‐years (QALYs) for individuals with Type 1 diabetes at different baseline HbA_1c, BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per‐person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates.

Results

Modelled subjects with an HbA_1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per‐person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA_1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA_1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per‐person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per‐person net monetary benefit, and up to £197 for the avoidance of one non‐severe hypoglyceamic event.

Conclusions

Maintained reductions in HbA_1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.     

Recovery of pulmonary functions,exercise capacity,and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis

Background

Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health‐related quality of life (HRQoL) after hospital discharge.

Objectives

The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1‐ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011.

Patients and Methods

Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL_CO), and 6‐minute walk distance (6MWD) in the patients survived from H1N1‐ARDS were collected 1, 3, and 6 months post‐hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ).

Results

Nine survivors of H1N1‐ARDS in the study period were included. All these patients received 2 months’ pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), DL_CO, and 6MWD improved from 1 to 3 months post‐hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post‐discharge.

Conclusion

The impaired pulmonary functions and exercise capacity in the survivors of H1N1‐ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity.     

Inequalities in glycaemic control,hypoglycaemia and diabetic ketoacidosis according to socio‐economic status and area‐level deprivation in Type 1 diabetes mellitus: a systematic review

Aim

The aim of this systematic review was to examine the associations of individual‐level as well as area‐level socio‐economic status and area‐level deprivation with glycaemic control, hypoglycaemia and diabetic ketoacidosis in people with Type 1 diabetes mellitus.

Methods

Ovid MEDLINE was searched to identify relevant cohort, case‐control or cross‐sectional studies published between January 2000 and June 2015. Search results were screened by title, abstract and keywords to identify eligible publications. Decisions on inclusion or exclusion of full texts were made independently by two reviewers. The Newcastle‐Ottawa Scale was used to estimate the methodological quality of included studies. Quality assessment and extracted data of included studies were synthesized narratively and reported according to the PRISMA statement.

Results

Literature search in Ovid MEDLINE identified 1345 eligible studies. Twenty studies matched our inclusion and exclusion criteria. Two articles were additionally identified through hand search. According to the Newcastle‐Ottawa Scale, most of the studies were of average quality. Results on associations of socio‐economic status and area‐level deprivation with glycaemic control and hypoglycaemia were contradictory between studies. By contrast, lower socio‐economic status and higher area‐level deprivation were associated with a higher risk for diabetic ketoacidosis in all except one study.

Conclusions

Lower socio‐economic status and higher area‐level deprivation are associated with a higher risk of experiencing diabetic ketoacidosis in people with Type 1 diabetes mellitus. Access to care for socially deprived people needs to be expanded to overcome impairing effects on the course of the condition and to reduce healthcare disparities.     

Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm

Aim

To identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm.

Materials and Methods

Data from adults and children with type 1 diabetes and more than two diabetes-related visits were analysed from the Diabetes Prospective Follow-up Registry. Q-Finder, a supervised non-parametric proprietary subgroup discovery algorithm, was used to identify subgroups with clinical characteristics associated with increased DKA risk. DKA was defined as pH less than 7.3 during a hospitalization event.

Results

Data for 108 223 adults and children, of whom 5609 (5.2%) had DKA, were studied. Q-Finder analysis identified 11 profiles associated with an increased risk of DKA: low body mass index standard deviation score; DKA at diagnosis; age 6-10 years; age 11-15 years; an HbA1c of 8.87% or higher (≥ 73 mmol/mol); no fast-acting insulin intake; age younger than 15 years and not using a continuous glucose monitoring system; physician diagnosis of nephrotic kidney disease; severe hypoglycaemia; hypoglycaemic coma; and autoimmune thyroiditis. Risk of DKA increased with the number of risk profiles matching patients’ characteristics.

Conclusions

Q-Finder confirmed common risk profiles identified by conventional statistical methods and allowed the generation of new profiles that may help predict patients with type 1 diabetes who are at a greater risk of experiencing DKA.     

The shape of the metabolic memory of HbA1c: re-analysing the DCCT with respect to time-dependent effects

Aims/hypothesis  

We determined the shape of the metabolic memory of HbA_1c and its contribution to retinopathy, as well as the importance of reducing HbA_1c to prevent progression of retinopathy.     

The use of metformin in type 1 diabetes: a systematic review of efficacy

Aims/hypothesis  

As adding metformin to insulin therapy has been advocated in type 1 diabetes, we conducted a systematic review of published clinical trials and clinical trial databases to assess the effects on HbA_1c, weight, insulin-dose requirement and adverse effects.     

Expert opinion on immunotherapy induced diabetes

Immunotherapy often incurs side-effects, mainly involving the skin, digestive tract and endocrine system. The most frequent endocrine side-effects involve the pituitary and thyroid glands. Cases of insulin-dependent diabetes, whether autoimmune or not (type 1 or 1B) have been reported with PD-1/PD-L1 inhibitors, alone or in association with anti-CTLA-4 antibodies, and were systematically associated with sudden-onset insulinopenia, frequently leading to ketoacidosis or fulminant diabetes, requiring first-line insulin therapy. This adverse effect has not so far been reported with anti-CTLA-4 monotherapy.Recommendations

• •R1. In patients receiving anti-PD-1 or anti-PD-L1 treatment, blood glucose should be assayed immediately in case of onset of polyuropolydipsic syndrome, weight loss or clinical signs of ketoacidosis, with HbA_1c assay in case of pathologic findings. Anti-GAD antibodies should be screened for in first line, to establish the auto-immune origin of the diabetes; if absent, anti-IA2 and anti-ZnT8 antibodies may be screened for. Blood lipase should be assayed in clinical fulminant diabetes. Pancreatic imaging is not indicated at diagnosis.
• •R2. As anti-PD-1/PD-L1-induced diabetes may be fulminant, with severe insulinopenia, emergency first-line multi-injection insulin therapy should be initiated, with treatment and education in a specialized center or by a mobile diabetology team. The HbA_1c target is < 8.0%. There are no other treatment options for immunotherapy-induced diabetes.
• •R3. Onset of diabetes under anti-PD-1 or anti-PD-L1 immunotherapy does not contraindicate continuation of treatment, although it may be interrupted for a few days in severe situations.
• •R4. Systematic fasting glucose and HbA_1C assay is recommended ahead of any anti-PD-1 or anti-PD-L1 immunotherapy, to screen for pre-existing diabetes, defined by fasting glucose > 1.26 g/L, and/or glycemia > 2 g/L at any time of day in case of polyuria, and/or HbA_1C ≥ 6.5%.
• •R5. Education should be ensured for patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy, to recognize inaugural symptoms of diabetes (polyuropolydipsic syndrome, weight loss) or ketoacidosis (vomiting, digestive disorder).
• •R6. In patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy, fasting glucose should be assayed at each course of treatment during the first 3 months, then every 3 months or urgently in case of onset of clinical signs.
• •R7. In case of diabetes pre-existing anti-PD-1 or anti-PD-L1 immunotherapy, glucose self-monitoring may be proposed or reinforced if already implemented.
• •R8. In view of the definitive nature of the induced diabetes, treatment and monitoring should be continued after the end of immunotherapy.
• •R9. Glucose monitoring is not recommended in anti-CTLA-4 therapy without associated anti-PD-1/PD-L1.

     

Associations of HbA1c and educational level with risk of cardiovascular events in 32 871 drug‐treated patients with Type 2 diabetes: a cohort study in primary care

Aims

To explore the association of HbA_1c and educational level with risk of cardiovascular events and mortality in patients with Type 2 diabetes.

Methods

A cohort of 32 871 patients with Type 2 diabetes aged 35 years and older identified by extracting data from electronic patient records for all patients who had a diagnosis of Type 2 diabetes and had glucose‐lowering agents prescribed between 1999 and 2009 at 84 primary care centres in Sweden. Associations of mean HbA_1c levels and educational level with risks of cardiovascular events and all‐cause mortality were analysed.

Results

The associations of HbA_1c with risk of all‐cause and cardiovascular mortality were J‐shaped, with the lowest risk observed for cardiovascular mortality at an HbA_1c level of 51 mmol/mol (6.8%) for subjects on oral agents and 56 mmol/mol (7.3%) in insulin‐treated patients. The lowest risk observed for all‐cause mortality was at an HbA_1c level of 51 mmol/mol (6.8%) for subjects on oral agents and 56 mmol/mol (7.3%) in insulin‐treated patients. There was an increased risk for cardiovascular death [hazard ratio 1.6 (1.2–2.1), P = 0.0008] at the lowest HbA_1c decile for subjects in the low education category. For subjects with higher education there was no evident J curve for cardiovascular death [hazard ratio 1.2 (0.8–1.6), P = 0.3873].

Conclusions

Our results lend support to the recent American Diabetes Association/ European Association for the Study of Diabetes position statement that emphasizes the importance of additional factors, including the propensity for hypoglycaemia, which should influence HbA_1c targets and treatment choices for individual patients. (Clinical Trials Registry No; NCT 01121315)     

Modelling incremental benefits on complications rates when targeting lower HbA1c levels in people with Type 2 diabetes and cardiovascular disease

Aim

Glucose‐lowering interventions in Type 2 diabetes mellitus have demonstrated reductions in microvascular complications and modest reductions in macrovascular complications. However, the degree to which targeting different HbA_1c reductions might reduce risk is unclear.

Methods

Participant‐level data for Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) participants with established cardiovascular disease were used in a Type 2 diabetes‐specific simulation model to quantify the likely impact of different HbA_1c decrements on complication rates. Ten‐year micro‐ and macrovascular rates were estimated with HbA_1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%) while holding other risk factors constant at their baseline levels. Cumulative relative risk reductions for each outcome were derived for each HbA_1c decrement.

Results

Of 5717 participants studied, 72.0% were men and 74.2% White European, with a mean (sd ) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9) mmHg, LDL‐cholesterol 2.3 (0.9) mmol/l, HDL‐cholesterol 1.13 (0.3) mmol/l and median Type 2 diabetes duration 9.6 (5.1–15.6) years. Ten‐year cumulative relative risk reductions for modelled HbA_1c values of 75, 64, 53 and 42 mmol/mol, relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and 46.4% for diabetes‐related ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation; and 13.6%, 25.4%, 36.0% and 44.7 for single‐eye blindness.

Conclusions

These simulated complication rates might help inform the degree to which complications might be reduced by targeting particular HbA_1c reductions in Type 2 diabetes.     

Short-term impact of HbA1c on morbidity and all-cause mortality in people with type 2 diabetes: a Danish population-based observational study

Aims/hypothesis  

In a population-based setting, we investigated whether diabetes-related morbidity and all-cause mortality within 2 years of HbA_1c measurement were associated with that HbA_1c level in individuals with type 2 diabetes. The main objective was to compare outcomes in those with HbA_1c ≥ and <7% (53 mmol/mol).     

Effets cardiovasculaires des auto-anticorps anti-récepteurs béta1 et béta3-adrénergiques chez le rat Lewis

Purpose

To analyze vascular reactivity changes in response to immunization protocols with antigens corresponding to the second extracellular loop of –β₃ and –β_1 and 3 adrenergic receptors (AR).

Methods

Lewis rats were immunized for 3 months with peptidic sequences corresponding to the second extracellular loop of β₃–AR or β_1 and 3–AR. Specific β₃–AR antibodies were characterized by Elisa and purified using “Proteus Protein G” kit. Their functionality were tested in rabbit isolated ventricular cardiomyocytes. Aortic and mesenteric artery rings isolated from control or immunized rats were mounted in organ baths and precontracted with phenylephrine. Then, relaxant curves were established.

Results

SR58611A (10 nM), a preferential β₃–AR agonist and purified β₃–AR antibodies (25 μg/mL) induced a decrease of cell shortening (−39.56 ± 4.4% [n = 11] and −18.45 ± 3.9% [n = 10] respectively) in isolated cardiomyocytes. This decrease was significantly inhibited when the cardiomyocytes were pre-incubated with the L–748337 (1 μM), a selective β₃–AR antagonist (P < 0.05). In contrast with what was observed in rats immunized against the β₁–AR, vasorelaxations induced by acetylcholine and SR58611A in both aorta and mesenteric arteries were unaltered in rats immunized against the β₃–AR and β_1 and 3–AR.

Conclusion

These results show, for the first time, that β₃–AR antibodies induced a β₃–AR agonist-like activity. They would not have a vascular pathogenic action but would offset the endothelial dysfunction caused by β₁–AR antibodies.     

Effects of finerenone in people with chronic kidney disease and type 2 diabetes are independent of HbA1c at baseline,HbA1c variability,diabetes duration and insulin use at baseline

Aim

To evaluate the effect of finerenone by baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use on cardiorenal outcomes and diabetes progression.

Materials and Methods

Composite efficacy outcomes included cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure), kidney (kidney failure, sustained ≥ 57% estimated glomerular filtration rate decline or renal death) and diabetes progression (new insulin initiation, increase in antidiabetic medication, 1.0% increase in HbA1c from baseline, new diabetic ketoacidosis diagnosis or uncontrolled diabetes).

Results

In 13 026 participants, risk reductions in the cardiovascular and kidney composite outcomes with finerenone versus placebo were consistent across HbA1c quartiles (P interaction .52 and .09, respectively), HbA1c variability (P interaction .48 and .10), diabetes duration (P interaction .12 and .75) and insulin use (P interaction .16 and .52). HbA1c variability in the first year of treatment was associated with a higher risk of cardiovascular and kidney events (hazard ratio [HR] 1.20; 95% confidence interval [CI] 1.07-1.35; P = .0016 and HR 1.36; 95% CI 1.21-1.52; P < .0001, respectively). There was no effect on diabetes progression with finerenone or placebo (HR 1.00; 95% CI 0.95-1.04). Finerenone was well-tolerated across subgroups; discontinuation and hospitalization because of hyperkalaemia were low.

Conclusions

Finerenone efficacy was not modified by baseline HbA1c, HbA1c variability, diabetes duration or baseline insulin use. Greater HbA1c variability appeared to be associated with an increased risk of cardiorenal outcomes.     

Haemoglobin A<Subscript>1c</Subscript> levels and subsequent cardiovascular disease in persons without diabetes: a meta-analysis of prospective cohorts

Aims/hypothesis  

The aim of this meta-analysis was to determine the relationship between HbA_1c levels and subsequent cardiovascular outcomes in individuals without diabetes.