Identification and comparison of insulin pharmacokinetics injected with a new 4‐mm needle vs 6‐ and 8‐mm needles accounting for endogenous insulin and C‐peptide secretion kinetics in non‐diabetic adult males

Aims/Introduction

Many patients with diabetes now use 5‐, 6‐ or 8‐mm needles for insulin injection. However, it is unclear whether needle length, particularly for shorter needles, affects the pharmacokinetic properties of insulin.

Materials and Methods

This was a three‐way, randomized, cross‐over, single‐center study involving 12 healthy Japanese adult males (age 27.4 ± 4.14 years; weight 64.2 ± 5.2 kg; body fat percentage 18.2 ± 1.5%). Participants received a subcutaneous (abdomen) dose of insulin lispro (1.5 U for participants weighing 55 to <65.0 kg; 2.0 U for participants weighing 65.0 to <80.0 kg) delivered using a 32‐G × 4 mm (32G × 4), 31‐G × 8 mm (31G × 8) or 32‐G × 6 mm (32G × 6) needle with a 3–7‐day washout between doses. Pharmacokinetic parameters of exogenous insulin were identified using non‐linear least squares, where the total insulin concentration was fit to the measured plasma insulin concentration using an overall combined model that accounted for C‐peptide/insulin secretion in addition to the injected dose.

Results

Maximum concentration and area under the curve for 0 to infinity min for insulin were bioequivalent for the 32G × 4 needle relative to the 32G × 6 and the 31G × 8 needles. The time to the maximum insulin concentration was bioequivalent for the 32G × 4 needle relative to the 32G × 6 needle, but not the 31G × 8 needle.

Conclusions

The use of 4‐mm needles is unlikely to change the pharmacokinetic properties of insulin when injected subcutaneously in adults. This trial was registered with UMIN‐CTR (no. UMIN000004469).     

Measurements of immature platelets with haematology analysers are of limited value to separate immune thrombocytopenia from bone marrow failure

Detection of immature platelets in the circulation may help to dissect thrombocytopenia due to platelet destruction from bone marrow failure (BMF ). We prospectively tested the predictive value of immature platelets, measured as immature platelet fraction (IPF ) on the XE‐5000 (Sysmex, Kobe, Japan) or percentage of reticulated platelets (rPT ) on the CD Sapphire (Abbott Diagnostics, Santa Clara, CA, USA) to separate immune thrombocytopenia (ITP ) from BMF (leukaemia, myelodysplastic syndrome, aplastic anaemia). We analysed 58 samples of patients with BMF , 47 samples of patients with ITP and 97 controls. Median rPT (CD Sapphire) was increased to 9·0% in ITP and to 10·9% in BMF , compared to 1·9% in controls. Median IPF (XE‐5000) was 16·2% in ITP , 10·2% in BMF and 2·5% in controls. We found an inverse correlation between high fractions of immature platelets and low platelet counts in thrombocytopenic samples regardless of the diagnosis. In conclusion, we observed a broad overlap of immature platelets between ITP and BMF , which may be caused by an accelerated release of immature platelets in any thrombocytopenic state and decreased production in many patients with ITP . Despite this, IPF (XE‐5000) had some power to discriminate ITP from BMF , whereas rPT (CD Sapphire) was of no predictive value.     

Advances in understanding the pathogenesis of familial myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are generally acquired as a result of a somatic stem cell mutation leading to clonal expansion of myeloid precursors. In addition to sporadic cases, familial MPN occurs when one or several MPN affect different relatives of the same family. MPN driver mutations (JAK2, CALR, MPL) are somatically acquired also in familial cases, so a genetic predisposition to acquire one of the MPN driver mutations would be inherited, even though the causative germline mutations underlying familial MPN remain largely unknown. Recently some germline variants [ATG2B and GSKIP duplication, RBBP6 mutations, SH2B3 (LNK) mutations], which can cause familial MPN, have been reported but these mutations are rare and do not explain most familial cases. Patients with familial MPN show the same clinical features and suffer the same complications as those with sporadic disease. This review aims to offer up‐to‐date information regarding the genetics of familial MPN.     

Type 2 diabetes in young adults in Central Auckland: demography and complications

Background

Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications.

Aims

To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration.

Methods

In total, 310 young adults with T2D (<40 years) were registered with the Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications.

Results

Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand‐born Pāsifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty‐four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4–5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001).

Conclusions

New migrants, New Zealand‐born Pāsifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications.     

Do medical oncology patients and their support persons agree about end‐of‐life issues?

Background

The perceptions of those called on to make decisions on behalf of patients who lack capacity at the end of life must accurately reflect patient preferences.

Aims

To establish the extent to which the views of medical oncology outpatients are understood by their support persons, specifically with regards to (i) preferred type and location of end‐of‐life care, (ii) preferred level of involvement in end‐of‐life decision‐making and (iii) whether the patient has completed an advance care plan or appointed an enduring guardian.

Methods

Adults with a confirmed cancer diagnosis and their nominated support persons were approached between September 2015 and January 2016 in the waiting room of an Australian tertiary referral clinic. Consenting participants completed a pen‐and‐paper survey. Nominated support persons answered the same questions from the patient’s perspective.

Results

In total, 208 participants (39% of eligible dyads) participated. Observed agreement across the five outcomes ranged from 54% to 84%. Kappa values for concordance between patient–support person responses were fair to moderate (0.24–0.47) for enduring guardian, decision‐making, advance care plan and care location outcomes. A slight level of concordance (k = 0.15; 95% confidence interval: ?0.02, 0.32) was found for the type of care outcome.

Conclusion

Relying on support persons’ views does not guarantee that patients’ actual preferences will be followed. Strategies that make patient preferences known to healthcare providers and support persons while they still have the capacity to do so is a critical next step in improving quality cancer care.     

Family history of diabetes,lifestyle factors,and the 7‐year incident risk of type 2 diabetes mellitus in middle‐aged Japanese men and women

Aims/Introduction

This cohort study of middle‐aged Japanese participants investigated the relationship between family history of diabetes, the incident risk of type 2 diabetes and the interaction of these variables with other factors.

Materials and Methods

Study participants were 3,517 employees (2,037 men and 1,480 women) of a metal products factory in Japan. Baseline health examinations included questions about medical history, physical examination, anthropometric measurements, questions about lifestyle factors, such as smoking, alcohol consumption and habitual exercise, and a self‐administered diet history questionnaire. Family history of diabetes was defined as having at least one‐first‐degree relative with diabetes. The incidence of diabetes was determined in annual medical examinations over a 7‐year period. Hazard ratios (HRs) for type 2 diabetes were estimated by Cox proportional hazards analysis.

Results

Of the 3,517 participants, 630 (18%) had a family history of diabetes mellitus. During the study, 228 participants developed diabetes. The age and sex‐adjusted HR for type 2 diabetes in participants with a family history of diabetes was 1.82 (95% confidence interval 1.36–2.43) as compared with those without a family history of diabetes. HRs did not change after adjustment for body mass index and lifestyle factors. We found no interactions with body mass index, insulin resistance, pancreatic β‐cell function or lifestyle factors.

Conclusions

Family history of diabetes was associated with the incident risk of diabetes, and these associations were independent of other risk factors, such as obesity, insulin resistance, and lifestyle factors in Japanese men and women.