Insulin Therapy in Type 2 Diabetes Is Associated With Barriers to Activity and Worse Health Status: A Cross-Sectional Study in Primary Care.

Introduction: Many individuals with type 2 diabetes mellitus (T2DM) experience "psychological insulin resistance". Consequently, it could be expected that insulin therapy may have negative effects on psychological outcomes and well-being. Therefore, this study compared health status and psychosocial functioning of individuals with T2DM using only oral antihyperglycemic agents (OHA) and on insulin therapy (with or without OHA). Materials and Methods: In this cross-sectional study, we used baseline data of a cluster randomized controlled trial conducted in 55 Dutch general practices in 2005. Health status was measured with the Short Form (SF)-36 (scale 0-100) and psychosocial functioning with the Diabetes Health Profile (DHP, scale 0-100). To handle missing data, we performed multiple imputation. We used linear mixed models with random intercepts per general practice to correct for clustering at practice level and to control for confounding. Results: In total, 2,794 participants were included in the analysis, their mean age was 65.8 years and 50.8% were women. Insulin-users (n = 212) had a longer duration of T2DM (11.0 versus 5.6 years) and more complications. After correcting for confounders and multiple comparisons, insulin-users reported significantly worse outcomes on vitality (SF-36, adjusted difference -5.7, p=0.033), general health (SF-36, adjusted difference -4.8, p=0.043), barriers to activity (DHP, adjusted difference -7.2, p<0.001), and psychological distress (DHP, adjusted difference -3.7, p=0.004), all on a 0-100 scale. Discussion: While previous studies showed similar or better health status in people with type 2 diabetes receiving insulin therapy, we found that vitality, general health and barriers to activity were worse in those on insulin therapy. Although the causality of this association cannot be established, our findings add to the discussion on the effects of insulin treatment on patient-reported outcomes in daily practice.

[Discontinuation of SSRIs and SNRIs]. / Het afbouwen van SSRI's en SNRI's.

Interruption or abrupt discontinuation of the use of antidepressants may lead to withdrawal symptoms. These are most common with selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs).There is insufficient scientific evidence about the prevalence of antidepressant withdrawal symptoms and how to optimally discontinue antidepressants. The multidisciplinary document 'Discontinuation of SSRIs & SNRIs' offers a rationale and suggestions for the gradual tapering of these antidepressants. The following factors are consistently named as risk factors for the occurrence of withdrawal symptoms: (a) the patient experiences withdrawal symptoms in case of non-compliance or skipped doses; (b) a previous attempt to stop was unsuccessful; and (c) the patient is being treated with higher doses than the smallest effective dose of SSRIs or SNRIs. In patients with one or more risk factors, a tapering schedule with non-linear dose-reduction steps should be considered. The speed at which these steps are taken, should be adjusted depending on occurrence of withdrawal symptoms. Shared decision-making by patient and physician is the best way to select a tapering schedule.

Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control.

BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of articles. The date of the last search was November 2015 for all databases. SELECTION CRITERIA: Randomised controlled clinical trials of at least two months' duration comparing insulin monotherapy with combinations of insulin with one or more oral glucose-lowering agent in people with type 2 diabetes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated overall quality of the evidence using GRADE. We summarised data statistically if they were available, sufficiently similar and of sufficient quality. We performed statistical analyses according to the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included 37 trials with 40 treatment comparisons involving 3227 participants. The duration of the interventions ranged from 2 to 12 months for parallel trials and two to four months for cross-over trials.The majority of trials had an unclear risk of bias in several risk of bias domains. Fourteen trials showed a high risk of bias, mainly for performance and detection bias. Insulin monotherapy, including once-daily long-acting, once-daily intermediate-acting, twice-daily premixed insulin, and basal-bolus regimens (multiple injections), was compared to insulin in combination with sulphonylureas (17 comparisons: glibenclamide = 11, glipizide = 2, tolazamide = 2, gliclazide = 1, glimepiride = 1), metformin (11 comparisons), pioglitazone (four comparisons), alpha-glucosidase inhibitors (four comparisons: acarbose = 3, miglitol = 1), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) (three comparisons: vildagliptin = 1, sitagliptin = 1, saxagliptin = 1) and the combination of metformin and glimepiride (one comparison). No trials assessed all-cause mortality, diabetes-related morbidity or health-related quality of life. Only one trial assessed patients' treatment satisfaction and showed no substantial differences between the addition of either glimepiride or metformin and glimepiride to insulin compared with insulin monotherapy.Insulin-sulphonylurea combination therapy (CT) compared with insulin monotherapy (IM) showed a MD in glycosylated haemoglobin A1c (HbA1c) of -1% (95% confidence interval (CI) -1.6 to -0.5); P < 0.01; 316 participants; 9 trials; low-quality evidence. Insulin-metformin CT compared with IM showed a MD in HbA1c of -0.9% (95% CI -1.2 to -0.5); P < 0.01; 698 participants; 9 trials; low-quality evidence. We could not pool the results of adding pioglitazone to insulin. Insulin combined with alpha-glucosidase inhibitors compared with IM showed a MD in HbA1c of -0.4% (95% CI -0.5 to -0.2); P < 0.01; 448 participants; 3 trials; low-quality evidence). Insulin combined with DPP-4 inhibitors compared with IM showed a MD in HbA1c of -0.4% (95% CI -0.5 to -0.4); P < 0.01; 265 participants; 2 trials; low quality evidence. In most trials the participants with CT needed less insulin, whereas insulin requirements increased or remained stable in participants with IM.We did not perform a meta-analysis for hypoglycaemic events because the included studies used different definitions.. In most trials the insulin-sulphonylurea combination resulted in a higher number of mild episodes of hypoglycaemia, compared to the IM group (range: 2.2 to 6.1 episodes per participant in CT versus 2.0 to 2.6 episodes per participant in IM; low-quality evidence). Pioglitazone CT also resulted in more mild to moderate hypoglycaemic episodes compared with IM (range 15 to 90 episodes versus 9 to 75 episodes, respectively; low-quality evidence. The trials that reported hypoglycaemic episodes in the other combinations found comparable numbers of mild to moderate hypoglycaemic events (low-quality evidence).The addition of sulphonylureas resulted in an additional weight gain of 0.4 kg to 1.9 kg versus -0.8 kg to 2.1 kg in the IM group (220 participants; 7 trials; low-quality evidence). Pioglitazone CT caused more weight gain compared to IM: MD 3.8 kg (95% CI 3.0 to 4.6); P < 0.01; 288 participants; 2 trials; low-quality evidence. Metformin CT was associated with weight loss: MD -2.1 kg (95% CI -3.2 to -1.1), P < 0.01; 615 participants; 7 trials; low-quality evidence). DPP-4 inhibitors CT showed weight gain of -0.7 to 1.3 kg versus 0.6 to 1.1 kg in the IM group (362 participants; 2 trials; low-quality evidence). Alpha-glucosidase CT compared to IM showed a MD of -0.5 kg (95% CI -1.2 to 0.3); P = 0.26; 241 participants; 2 trials; low-quality evidence.Users of metformin CT (range 7% to 67% versus 5% to 16%), and alpha-glucosidase inhibitors CT (14% to 75% versus 4% to 35%) experienced more gastro-intestinal adverse effects compared to participants on IM. Two trials reported a higher frequency of oedema with the use of pioglitazone CT (range: 16% to 18% versus 4% to 7% IM). AUTHORS' CONCLUSIONS: The addition of all oral glucose-lowering agents in people with type 2 diabetes and inadequate glycaemic control who are on insulin therapy has positive effects on glycaemic control and insulin requirements. The addition of sulphonylureas results in more hypoglycaemic events. Additional weight gain can only be avoided by adding metformin to insulin. Other well-known adverse effects of oral glucose-lowering agents have to be taken into account when prescribing oral glucose-lowering agents in addition to insulin therapy.

[Summary of the Dutch College of General Practitioners' (NHG) practice guideline 'ADHD in children']. / Samenvatting van de NHG-standaard 'ADHD bij kinderen'.

The diagnosis of ADHD may be considered if a child is hyperactive, impulsive or inattentive, and if this behaviour results in evidently impaired functioning in multiple settings. Children with behavioural problems and slightly impaired functioning may benefit from patient information, education and parenting advice. From the age of 6 years, children can be offered diagnostic testing and professional support within the primary care setting, provided sufficient knowledge and expertise is available and there is collaboration with other health care providers. Management of a child with ADHD but no comorbid psychiatric disorder, consists of a step-by-step plan including education, parent and teacher guidance and, optionally, behavioural therapy for the child. In consultation with parents, child and other therapists, methylphenidate can be prescribed if behavioural interventions are not sufficiently effective. Children taking medication for ADHD should be monitored periodically, including assessment of the effectiveness and side effects.

[Summary of the Dutch College of General Practitioners' practice guideline 'Depression']. / Samenvatting van de NHG-Standaard 'Depressie'.

This guideline gives recommendations for the management of depression and depressive symptoms. The diagnosis of suspected depression requires a broad exploration of symptoms, sometimes over several visits. The guideline promotes self-management and patient empowerment during the healing process. The initial step in the treatment of depressive symptoms is patient education; patients with depression are supported with activity scheduling and are offered a short course of psychological treatment. If the initial treatment in patients with depression is not effective or if the depression is associated with severe suffering, severe social dysfunctioning or severe psychiatric comorbidity, psychotherapy or an antidepressant is recommended.

[Summarisation of the NHG practice guideline 'Anxiety']. / Samenvatting van de NHG-standaard 'Angst'.

Anxiety and anxiety disorders are addressed in the practice guideline of the Dutch College of General Practitioners (NHG). It is important to distinguish anxiety and anxiety disorders because of differences in prognosis and treatment. Several visits may be needed before the diagnosis is established. Treatment is based on a stepped-care model. For anxiety, psychoeducation and follow-up visits are often sufficient. For anxiety disorders with relatively low levels of distress or social dysfunctioning, self-help with supervision in addition to psychoeducation is helpful. If this is not effective or if there is severe distress or social dysfunctioning, cognitive behavioural therapy is the first choice treatment. An antidepressant could be started after or in addition to cognitive behavioural therapy. If an antidepressant is prescribed, SSRIs are preferred above tricyclic antidepressants because of the lesser risk of severe adverse effects.

Primary care and public health a natural alliance? The introduction of the guidelines for obesity and undernutrition of the Dutch College of General Practitioners.

The prevalence of obesity and overweight is increasing globally and forms a huge public health problem. On the other hand, the prevalence of malnutrition or undernutrition is substantial, especially in nursing homes or in the elderly at home. Primary care and public health are separate disciplines. But in the field of nutrition and other lifestyle-related interventions, there are many direct and indirect interfaces for over- as well as undernutrition. The Dutch College of General Practitioners (NHG) published the Practice Guideline Obesity in adults and children to lead GPs in this process and to bridge the gap with public health. The same applies for the recently published National Primary Care Cooperation Agreement Undernutrition on the collaboration of primary care workers to enhance awareness and early intervention in case of nutritional impairment. This article goes into the background as well as the content of these two NHG products and the implications for daily practice. An attempt is made to connect primary care and public health in this matter. Particularly in the case of obesity, a close relationship with public health is of vital importance.

[Summary of the Dutch College of General Practitioners' practice guidelines on obesity]. / Samenvatting van de standaard 'Obesitas' van het Nederlands Huisartsen Genootschap.

Adults with obesity have a decreased life expectancy and an increased risk of disease. Preferred treatment is a combination of lifestyle interventions, consisting of changes in diet, physical exercise and psychological support. Normal weight is not an achievable target in most adults, but even a 5-10% weight loss yields significant health gains. Obese children run a significant risk of mental and physical illness and often become obese adults. Indeed, the practice guidelines recommend an active approach by the general practitioner if a child appears obese at a consultation, irrespective of the reason for consultation.

Insulin therapy in type 2 diabetes: what is the evidence?

AIM: To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus METHODS: A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. RESULTS: The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long-acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long-acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal-bolus regimen seems not possible. Some studies showed that rapid-acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. CONCLUSION: A once-daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years.

Insulin therapy in type 2 diabetes is no longer a secondary care activity in the Netherlands.

AIM: Because Dutch health care organisations did want to establish well-defined diabetes shared care groups, we investigated the organisation of insulin therapy in general practice in the Netherlands and assessed factors that were associated with providing insulin therapy in type 2 diabetes (DM2) patients. METHODS: Questionnaire to half of the Dutch general practitioners (GPs) (n=3848). We compared GPs who both start insulin treatment and monitor the dosages with those who always refer patients requiring insulin therapy or only monitor insulin dosages. RESULTS: Total response was 42% (n=1621). 67% of the GPs start insulin therapy in patients with DM2, especially male GPs and those above the age of 40, as well as GPs working in a health centre and those working together with a practice nurse. GPs working in urban regions less often start insulin. The most often mentioned barriers for starting and/or monitoring insulin therapy are lack of knowledge of insulin therapy, lack of time and insufficient financial incentives. CONCLUSION: This nation-wide overview shows that insulin therapy is no longer a secondary care based activity. However, there is still need to enlarge the practice staff and to overcome the perceived skills deficit.