Keeping safe. Continuous glucose monitoring (CGM) in persons with Type 1 diabetes and impaired awareness of hypoglycaemia: a qualitative study.

AIM: To further our understanding of individual use and experience of continuous glucose monitoring (CGM) in adults with Type 1 diabetes and impaired awareness of hypoglycaemia, we conducted a qualitative study supplementary to a randomized controlled trial, using semi-structured interviews. METHODS: Twenty-three participants of the IN CONTROL trial were interviewed within 4 weeks after the last study visit. The interview centred around experiences of CGM, taking into account the person's expectations prior to the trial. The interview was semi-structured, using open-ended questions and, if needed, prompts were offered to elicit further responses. Using thematic analysis, the interview transcripts were coded independently by three members of the research team. The consolidated criteria for reporting qualitative research (COREQ) were followed. RESULTS: Overall, CGM was experienced as helpful in gaining more insight into glucose variability, and temporarily improved sense of control, reduced distress and made participants less dependent on others. However, some participants experienced confrontation with CGM output as intrusive, while some reported frustration due to failing technique and difficulty trusting the device. Participants reported active and passive self-management behaviours mirroring individual differences in attitudes and coping styles. CONCLUSIONS: In adults with Type 1 diabetes at risk of recurrent hypoglycaemia due to impaired awareness of hypoglycaemia, CGM use enhances a sense of control and safety for most, but not all. Future studies should further explore differential use of CGM in this population in the context of active and passive self-management styles.

Diabetes-specific emotional distress in people with Type 2 diabetes: a comparison between primary and secondary care.

AIMS: To compare levels of diabetes distress in people with Type 2 diabetes treated in primary and secondary care and to examine demographic and clinical correlates that may explain potential differences in levels of distress between care settings. METHODS: People with Type 2 diabetes from 24 primary care practices (n = 774) and three secondary care clinics (n = 526) completed the Problem Areas In Diabetes questionnaire. Data on HbA1c levels and diabetes complications were derived from medical charts. Hierarchical ordinal regression analysis was used to investigate which correlates could explain the potential differences in level of diabetes distress between care settings. RESULTS: Diabetes distress levels and the prevalence of elevated diabetes distress were considerably lower in the participants treated in primary care (mean (SD) total diabetes distress score 8 (11); 4% of participants with a Problem Areas In Diabetes score ≥ 40) than in secondary care (mean (SD) total diabetes distress score 23 (21); 19% of participants with a Problem Areas In Diabetes score ≥ 40, P < 0.001). In addition to care setting, the following variables were also independently related to diabetes distress: younger age, ethnic minority status, using insulin, having a higher HbA1c level, having a higher BMI and the presence of neuropathy. Other diabetes complications were not independently associated with diabetes distress. CONCLUSIONS: In primary care, lower levels of diabetes distress were reported than in secondary care. The difference in diabetes distress between care settings can be largely, but not fully, explained by specific demographic and clinical characteristics. These results need to be interpreted with caution as they are based on two separate studies, but do call into question the need to screen for diabetes distress in people with Type 2 diabetes in primary care.

Differential associations between depressive symptoms and glycaemic control in outpatients with diabetes.

AIMS: Depression is common in people with diabetes, and related to higher HbA(1c) levels. Depression, however, is a heterogeneous construct that involves a variety of symptoms. As little is known about the associations of individual depressive symptoms with HbA(1c), we explored these associations in outpatients with diabetes. METHODS: The study was conducted in three tertiary diabetes clinics in the Netherlands. At baseline, the presence of the nine depressive symptoms that are listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was assessed with the nine-item Patient Health Questionnaire (PHQ-9). At baseline and after a 1-year follow-up, HbA(1c) was derived from the medical charts. RESULTS: A total of 288 out of 646 subjects with diabetes (45%) reported one or more depressive symptom(s). Depressed mood (ß = 0.11, P = 0.005), sleeping difficulties (ß = 0.16, P < 0.001), appetite problems (ß = 0.15, P < 0.001) and suicidal ideation (ß = 0.14, P = 0.001) were significantly related to higher baseline HbA(1c) values. Furthermore, depressed mood (ß = 0.09, P = 0.03) sleeping difficulties (ß = 0.12, P = 0.004), appetite problems (ß = 0.11, P = 0.01) and psychomotor agitation/retardation (ß = 0.09, P = 0.04) were significantly related to higher HbA(1c) values at 1-year follow-up. Associations were more pronounced in Type 1 diabetes than in Type 2 diabetes. None of the depressive symptoms were related to change in HbA(1c) over time, except suicidal ideation. CONCLUSION: In people with diabetes, several individual depressive symptoms were related to higher HbA(1c) levels. These associations persisted over time. More research is needed to investigate potential mechanistic pathways.

Psychometric and screening properties of the WHO-5 well-being index in adult outpatients with Type 1 or Type 2 diabetes mellitus.

OBJECTIVE: The 5-item World Health Organization well-being index is a commonly used measure of emotional well-being, but research on psychometric properties in outpatients with diabetes is scarce. We examined psychometric and screening properties for depression of this index in a large sample of Dutch outpatients with diabetes. METHODS: Patients with Type 1 (n = 384) and Type 2 (n = 549) diabetes from three outpatient clinics completed the WHO-5 index, the nine-item Patient Health Questionnaire, the Problem Areas in Diabetes survey and the Short Form-12 health survey. Internal consistency of the WHO-5 index was determined by Cronbach's alpha. The factor structure was tested by confirmatory factor analysis. Concurrent validity was assessed by correlations with the Patient Health Questionnaire, Problem Areas in Diabetes and the Short Form-12 mental component scores. Sensitivity and specificity of the WHO-5 index as depression screener were tested against two existing Patient Health Questionnaire cut-off scores for depression using receiver operating characteristic curves. RESULTS: A one-factor structure of the WHO-5 index was verified by confirmatory factor analysis for patients with Type 1 and Type 2 diabetes. Moderate to strong correlations were observed between the WHO-5 index and the Patient Health Questionnaire scores, the Problem Areas in Diabetes scores and the Short Form-12 mental component scores (r = 0.55-0.69, P < 0.001). Receiver operating characteristic curves showed that a WHO-5 index cut-off of < 50 performed best as an indication for likely depression, with sensitivity compared with a Patient Health Questionnaire score ≥ 10 and ≥ 12 of 79% and 88%, respectively, and specificity of 88% and 76%, respectively. CONCLUSIONS: The WHO-5 index is a short, psychometrically sound measure of emotional well-being that appears suitable for use as screening test for likely depression in outpatients with Type 1 and Type 2 diabetes.

Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study.

AIMS/HYPOTHESIS: Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. METHODS: Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes. RESULTS: Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified. CONCLUSION/INTERPRETATION: Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin.

Limited effect of screening for depression with written feedback in outpatients with diabetes mellitus: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to test the effectiveness of a screening procedure for depression (SCR) vs care as usual (CAU) in outpatients with diabetes. The primary outcome measured was depression score and the secondary outcomes were mental healthcare consumption, diabetes-distress and HbA(1c). MATERIALS AND METHODS: In a multicentre parallel randomised controlled trial, 223 outpatients with diabetes, who had an elevated depression score, were randomly assigned to SCR (n = 116) or CAU (n = 107), using computer generated numbers. SCR-patients were invited for a Composite International Diagnostic Interview (CIDI) to diagnose depression and/or anxiety (interviewers were not blinded for group assignment). As part of the intervention, patients and their physicians were informed of the outcome of the CIDI in a letter and provided with treatment advice. At baseline and 6 month follow-up, depression and diabetes-distress were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Problem Areas in Diabetes survey (PAID). HbA(1c) levels were obtained from medical charts. RESULTS: Mean CES-D depression scores decreased from baseline to 6 months in both groups (24 ± 8 to 21 ± 8 [CAU] and 26 ± 7 to 22 ± 10 [SCR] respectively [p < 0.001]), with no significant differences between groups. Neither diabetes-distress nor HbA(1c) changed significantly within and between groups. The percentage of patients receiving mental healthcare increased in the SCR group from 20% to 28%, compared with 15% to 18% in the CAU group. CONCLUSIONS/INTERPRETATION: Depression screening with written feedback to patient and physician does not improve depression scores and has a limited impact on mental healthcare utilisation, compared with CAU. It appears that more intensive depression management is required to improve depression outcomes in patients with diabetes.

Diabetes-specific emotional distress mediates the association between depressive symptoms and glycaemic control in Type 1 and Type 2 diabetes.

OBJECTIVES: To investigate whether diabetes-specific emotional distress mediates the relationship between depression and glycaemic control in patients with Type 1 and Type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were derived from the baseline assessment of a depression in diabetes screening study carried out in three tertiary diabetes clinics in the Netherlands. Most recent glycated haemoglobin (HbA(1c)) measurement was obtained from medical records. The Centre for Epidemiologic Studies Depression Scale (CES-D) and Problem Areas in Diabetes scale (PAID) were used to measure depression and diabetes-specific emotional distress respectively. Linear regression was performed to examine the mediating effect of diabetes-distress. RESULTS: Complete data were available for 627 outpatients with Type 1 (n = 280) and Type 2 (n = 347) diabetes. Analyses showed that diabetes-distress mediated the relation between depression and glycaemic control and not differently for both disease types. Post-hoc analyses revealed that patients depressed and distressed by their diabetes were in significantly poorer glycaemic control relative to those not depressed nor distressed (HbA(1c) 8.7 +/- 1.7 vs. 7.6 +/- 1.2% in those without depressive symptoms, 7.6 +/- 1.1% in depressed only and 7.7 +/- 1.1% in the distressed only, P < 0.001). Depressed patients without elevated diabetes-distress did not show a significantly increased risk of elevated HbA(1c). CONCLUSIONS: In explaining the association between depression and glycaemic control, diabetes-specific emotional distress appears to be an important mediator. Addressing diabetes-specific emotional problems as part of depression treatment in diabetes patients may help improve glycaemic outcomes.

Prevalence of comorbid depression is high in out-patients with Type 1 or Type 2 diabetes mellitus. Results from three out-patient clinics in the Netherlands.

AIMS: Depression is common in diabetes, but the scope of the problem and associated correlates are not well established in specialist diabetes care. We aimed to determine the prevalence of depression among adult outpatients with Type 1 (T1DM) or Type 2 diabetes (T2DM) using both self-report measures and a diagnostic interview, and to establish demographic and clinical characteristics associated with depressive affect. METHODS: A random sample of 2055 diabetes out-patients from three diabetes clinics was invited to participate. Depressive affect was assessed using the World Health Organization-5 Well Being Index (WHO-5), the Centre for Epidemiologic Studies-Depression scale (CESD) using predefined cut-off scores, and depressive disorder with the Composite International Diagnostic Interview (CIDI). Associations between depression and patient characteristics were explored using regression analyses. RESULTS: Seven hundred and seventy-two patients completed the depression questionnaires. About one-third of T1DM patients and 37-43% of T2DM patients reported depressive affect (WHO-5). The prevalence of depressive affect (CESD) was 25% and 30% for men and women with T1DM, and 35% and 38% for men and women with T2DM, respectively. Based on the CIDI, 8% of T1DM patients (no gender difference) and 2% of men and 21% of women with T2DM suffered from a depressive disorder. Depressive affect was associated with poor glycaemic control and proliferative retinopathy in T1DM, while non-Dutch descent, obesity and neuropathy were correlates in T2DM. CONCLUSIONS: Depressive symptoms and major depressive disorder constitute a common comorbid problem among Dutch out-patients with T1DM or T2DM and appear particularly common in migrants and women with T2DM.

A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion.

AIM: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety. METHODS: In this open, randomized, controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized to CIPII or CSII. The aim was to obtain the best possible blood glucose while avoiding hypoglycemia. RESULTS: The frequency of any hypoglycemia was similar (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910). The incidence of severe hypoglycemia with CSII was more than twice the one with CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean blood glucose, and glucose fluctuations were not statistically different. Treatment-related severe complications occurred mainly during CIPII: port infections (0.47 events / patient year), abdominal pain (0.21 events / patient year), insulin underdelivery (0.14 events / patient year). Weight gain was greater with CSII (+ 1.5 kg vs. - 0.1 kg, p = 0.013), quality of life better with CIPII. CONCLUSIONS: In type 1 diabetes CIPII with DiaPort reduces the number of severe episodes of hypoglycemia and improves quality of life with no weight gain. Because of complications, indications for CIPII must be strictly controlled. CIPII with DiaPort is an alternative therapy when CSII is not fully successful and provides an easy method of intraperitoneal therapy.

Incretins: a new treatment option for type 2 diabetes?

This article describes how the discovery of a protein almost 100 years ago led to a clinical treatment for type 2 diabetes. Food intake, but also stimulation of the sympathetic nervous system (for example physical exercise), stimulates the secretion of glucagon-like-peptide-1 (GLP-1), derived from the glucagon precursor proglucagon in the small intestine. GLP-1 stimulates the production and secretion of insulin, the release of somatostatin, glucose utilisation by increasing insulin sensitivity and in animal studies also beta-cell function and expansion (proliferation). It inhibits glucagon release, gastric emptying, appetite and food intake via the central nervous system and in animal experiments also apoptosis of beta-cells. Since GLP-1 has to be administered parenterally and its half-life is short, a long-acting GLP-1 receptor agonist (exenatide) and a long-acting GLP-1 analogue (liraglutide) have been developed as well as an inhibitor of DPP-IV (the enzyme that breaks down endogenous GLP-1). Clinical studies with exenatide and liraglutide as monotherapy show a significant increase in the postprandial insulin concentration as well as a smaller increase in the postprandial glucose values. Adding these drugs to standard oral glucose-lowering medication shows improvement in glucose and insulin concentrations and HbA1c compared with adding placebo. The effect of exenatide on HbA1c is the same as adding a long-acting insulin analogue (glargine), but the increase in weight after adding insulin is not seen after exenatide, where even a small decrease in weight is found. This is an important advantage, because most type 2 patients are already obese. Whether less beta-cell apoptosis and maintenance of beta-cell function occurs, as has been shown in animal studies, has to be awaited. Clinical studies with the oral DPPIV inhibitors sitagliptin and vildagliptin show promising results, but are only published as abstracts at scientific meetings.

Castleman's disease: A rare lymphoproliferative disorder.

Castleman's disease (CD) is an atypical lymphoproliferative disorder. Since it was first described in 1956, it has been referred to as follicular lympho-reticuloma, angiofollicular mediastinal lymph node hyperplasia, and benign giant lymphoma. CD is a heterogeneous disease that can be either localized or systemic (multicentric). The localized form can be divided into two types: the hyaline-vascular (HV) type or the plasma cell (PC) type. The former usually produces few symptoms and histological features include abnormal follicles and increased interfollicular vascularity. The PC type, in which, histopathologically, the presence of sheets of mature plasma cells is the distinguishing feature, is more likely to produce clinical symptoms such as fever, night sweats, and lymphadenopathy. The multicentric form mimics the PC type of localized CD, and patients present with systemic symptoms. In this report, we discuss the spectrum of clinical and pathological findings in localized and multicentric CD.

Mural aortic thrombus and peripheral embolisation in a patient with hyperhomocysteinaemia.

A mobile thrombus of the descending thoracic aorta in young people is extremely uncommon. We describe a 38-year-old woman with a mural thrombus in the proximal aorta complicated by peripheral embolisation, due to hyperhomocysteinaemia.

[Diagnostic image (231). A woman with bluish sweat]. / Diagnose in beeld (231). Een vrouw met blauw zweet.

A 56-year-old woman had bluish discoloration of the upper part of white cotton underclothing, caused by apocrine chromhidrosis.

A 43-year-old male with untreated panhypopituitarism due to absence of the pituitary stalk: from dwarf to giant.

A 43-yr-old male was referred because of an x-ray made after a fall, which showed open epiphysis of the arm. The man had always been short for his age; during childhood he once consulted a pediatrician because of short stature, but thereafter he never sought medical attention. At age 18 yr he was not allowed to join the army because of his height of 147 cm. He continued to grow steadily and finally reached 193 cm. He had no complaints and considered himself reasonably fit. Physical examination showed a disproportional man with a body mass index of 29.3 kg/m(2) and Tanner stage P1G1. Laboratory investigations showed hormone levels consistent with multiple pituitary deficiency, with dynamic tests consistent with hypothalamic or pituitary stalk disease. Magnetic resonance scanning of the brain showed a small anterior pituitary remnant, no pituitary stalk, and an ectopic neurohypophysis. This case of untreated panhypopituitarism shows a particular growth curve with an average growth velocity of 2 cm/yr, resembling patients with estrogen receptor mutation or aromatase deficiency. A literature study of other adult patients with untreated panhypopituitarism shows a variable growth pattern. Some speculations about possible reasons for this variability in clinical characteristics are presented.

Effect of administration of growth hormone on plasma and intracellular levels of thyroxine and tri-iodothyronine in thyroidectomized thyroxine-treated rats.

We have studied the effects of the administration of GH on plasma levels and peripheral production of tri-iodothyronine (T3) from thyroxine (T4) in thyroidectomized male Wistar rats given a continuous i.v. infusion of T4 (1 microgram/100 g body weight per day) and GH (120 micrograms per day) for 3 weeks. Tracer doses of 131I-labelled T3 and 125I-labelled T4 were added to the infusion. At isotopic equilibrium (10 days after the addition of 125I-labelled T4) the rats were bled and perfused. The plasma appearance rate for T3 was higher (10.6 +/- 1.3 vs 8.4 +/- 2.8 pmol/h per 100 g body weight, P = 0.05) and plasma TSH was lower (246 +/- 24 vs 470 +/- 135 pmol/l, P less than 0.01) in GH-treated rats. The amount of T3 in liver (12.3 +/- 2.8 vs 5.5 +/- 1.7 pmol/g wet weight, P less than 0.01), kidney (11.5 +/- 1.4 vs 6.5 +/- 1.4 pmol/g wet weight, P less than 0.01) and pituitary (8.8 +/- 2.7 vs 4.8 +/- 0.5 pmol/g wet weight, P less than 0.01) was higher than in controls, mainly as a result of an increased local production of T3 from T4, but plasma-derived T3 was also higher in most organs. We found an increased intracellular T3 concentration in the pituitary which may be responsible for the lower plasma TSH concentration in the GH-treated rats. Since the increase in locally produced T3 is found particularly in liver, kidney and pituitary, typical organs that express 5'-deiodinase activity, we suggest that GH acts on thyroid hormone metabolism by stimulating type-I deiodinase activity.

[Shoshin beriberi provoked by the inhalation of salbutamol]. / Sjosjin-beriberi na inhalatie van salbutamol.

A 45-year-old male alcoholic with a deficient diet was given salbutamol for exertion-related dyspnoea. After inhalation, he presented with a severe dyspnoea, acrocyanosis, anuria and low blood pressure as well as a respiratory compensated lactate acidosis. Shoshin beriberi was suspected on clinical grounds. The low level of thiamine and the prompt recovery after thiamine repletion confirmed this diagnosis. Shoshin beriberi is an acute, cardiac form of beriberi, which can rapidly result in death due to cardiogenic shock and lactate acidosis. Adrenergic agents can cause a hyperdynamic circulation and thus aggravate the effects of a thiamine deficiency.