GLP-1 agonists for people living with HIV and obesity, is there a potential?

BACKGROUND AND OBJECTIVES: Obesity trends and metabolic dysregulation are rising in people living with HIV using antiretrovirals (ARVs). Underlying causes and preventive strategies are being investigated. Two glucagon like-peptide 1 (GLP-1) agonists, liraglutide and semaglutide, were formerly approved as glucose-lowering drugs and have been recently approved for long-term weight loss in people with obesity. Due to the lack of therapeutic guidelines or clinical trials in people with HIV, we discuss the potential benefits, safety aspects and pharmacological considerations of prescribing liraglutide and semaglutide in people with HIV. RESULTS: Clinical experience is limited to two clinical cases of diabetic people with HIV using liraglutide after which a successful weight loss and glycaemic control were observed. None of the adverse events associated with liraglutide and semaglutide usage indicate an additional risk for people with HIV. Extra caution showed be warranted when initiating GLP-1 agonist therapy in people with HIV taking protease inhibitors who have pre-existing risk factors for heart rate variability to reduce the incidence of RP interval prolongation. GLP-1 agonists are metabolized by endopeptidases, and thus do not generate major drug-drug interactions with most drugs, including ARVs. GLP-s agonists are known to inhibit gastric acid secretion, which warrants caution and close monitoring when combined with atazanavir and oral rilpivirine, two ARVs that require low gastric pH for an optimal absorption. CONCLUSION: Theoretical considerations and a few available clinical observations support semaglutide and liraglutide prescription in people with HIV, with, thus far, no indications of concern regarding efficacy, safety or pharmacological interactions with ARVs.

The challenge of choosing in cardiovascular risk management.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.

Characteristics associated with polypharmacy in people with type 2 diabetes: the Dutch Diabetes Pearl cohort.

AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.

[Starting insulin or not? And if so, which basal insulin?] / Geen insuline of toch wel? En welke dan?

A 55-year-old patient with a BMI of 30 kg/m2 is referred for uncontrolled type 2 diabetes mellitus. His HbA1c-concentration is 71 mmol/mol, despite an initial 8% weight loss and treatment with metformin and glimepiride. The general practitioner proposes to start with insulin, but the patient refuses. We discuss whether there is a good alternative for insulin such as more weight loss and the addition of more drugs. Our patient then changes his mind and agrees to start insulin treatment. Basal insulin is usually recommended in cases like this.Since there are no significant differences between different types of available basal insulin, it seems reasonable to take price into account. Our patient achieved reasonable glucose control without weight gain using a combination of basal insulin and a GLP-1 receptor agonist.

Reducing the burden of hypoglycaemia in people with diabetes through increased understanding: design of the Hypoglycaemia REdefining SOLutions for better liVEs (Hypo-RESOLVE) project.

BACKGROUND: Hypoglycaemia is the most frequent complication of treatment with insulin or insulin secretagogues in people with diabetes. Severe hypoglycaemia, i.e. an event requiring external help because of cognitive dysfunction, is associated with a higher risk of adverse cardiovascular outcomes and all-cause mortality, but underlying mechanism(s) are poorly understood. There is also a gap in the understanding of the clinical, psychological and health economic impact of 'non-severe' hypoglycaemia and the glucose level below which hypoglycaemia causes harm. AIM: To increase understanding of hypoglycaemia by addressing the above issues over a 4-year period. METHODS: Hypo-RESOLVE is structured across eight work packages, each with a distinct focus. We will construct a large, sustainable database including hypoglycaemia data from >100 clinical trials to examine predictors of hypoglycaemia and establish glucose threshold(s) below which hypoglycaemia constitutes a risk for adverse biomedical and psychological outcomes, and increases healthcare costs. We will also investigate the mechanism(s) underlying the antecedents and consequences of hypoglycaemia, the significance of glucose sensor-detected hypoglycaemia, the impact of hypoglycaemia in families, and the costs of hypoglycaemia for healthcare systems. RESULTS: The outcomes of Hypo-RESOLVE will inform evidence-based definitions regarding the classification of hypoglycaemia in diabetes for use in daily clinical practice, future clinical trials and as a benchmark for comparing glucose-lowering interventions and strategies across trials. Stakeholders will be engaged to achieve broadly adopted agreement. CONCLUSION: Hypo-RESOLVE will advance our understanding and refine the classification of hypoglycaemia, with the ultimate aim being to alleviate the burden and consequences of hypoglycaemia in people with diabetes.

Sweet dreams or bitter nightmare: a narrative review of 25 years of research on the role of sleep in diabetes and the contributions of behavioural science.

The aim of this review was to provide an overview of developments, clinical implications and gaps in knowledge regarding the relationship between diabetes and sleep over the past 25 years, with special focus on contributions from the behavioural sciences. Multiple prospective observational and experimental studies have shown a link between suboptimal sleep and impaired glucose tolerance, decreased insulin sensitivity and the development of type 2 diabetes. While prevalence rates of suboptimal sleep vary widely according to definition, assessment and sample, suboptimal subjective sleep quality appears to be a common reality for one-third of people with type 1 diabetes and over half of people with type 2 diabetes. Both physiological and psychosocial factors may impair sleep in these groups. In turn, suboptimal sleep can negatively affect glycaemic outcomes directly or indirectly via suboptimal daytime functioning (energy, mood, cognition) and self-care behaviours. Technological devices supporting diabetes self-care may have both negative and positive effects. Diabetes and its treatment also affect the sleep of significant others. Research on the merits of interventions aimed at improving sleep for people with diabetes is in its infancy. Diabetes and sleep appear to be reciprocally related. Discussion of sleep deserves a central place in regular diabetes care. Multi-day, multi-method studies may shed more light on the complex relationship between sleep and diabetes at an individual level. Intervention studies are warranted to examine the potential of sleep interventions in improving outcomes for people with diabetes.

Patients with type 1 diabetes mellitus have impaired IL-1ß production in response to Mycobacterium tuberculosis.

Patients with diabetes mellitus have an increased risk of developing tuberculosis. Although the underlying mechanism is unclear, evidence suggests a role for chronic hyperglycaemia. We examined the influence of hyperglycaemia on Mycobacterium tuberculosis-induced cytokine responses in patients with type 1 diabetes mellitus (T1D). Peripheral blood mononuclear cells (PBMCs) from 24 male T1D patients with sub-optimal glucose control [HbA1c > 7.0% (53 mmol/L)] and from 24 age-matched male healthy controls were stimulated with M. tuberculosis lysate. Cytokine analysis, assessment of aerobic glycolysis, receptor recognition and serum cross-over experiments were performed to explore the mechanistic differences. PBMCs from T1D patients produced less bioactive interleukin (IL)-1ß in response to M. tuberculosis. IL-6 and interferon (IFN)-γ production trended towards a decrease, whilst other cytokines such as tumour necrosis factor (TNF)-α, IL-17 and IL-1Ra were normal. The decrease in cytokine production was not correlated to HbA1c or plasma glucose levels. Cross-over serum experiments did not alter the cytokine profile of T1D or control patients, arguing for an intrinsic cellular defect. Cellular metabolism and the expression of M. tuberculosis-related pattern recognition receptors (PRRs) such as TLR2, TLR4 and NOD2 did not differ between T1D patients and healthy controls. Compared to matched controls, T1D patients have a reduced capacity to produce pro-inflammatory cytokines in response to M. tuberculosis. The impaired IL-1ß production in T1D patients may contribute to the increased susceptibility to tuberculosis. This effect appears not to be related to prevailing glucose levels but to an intrinsic cellular deficit.

A cost-controlling treatment strategy of adding liraglutide to insulin in type 2 diabetes.

BACKGROUND: Addition of the GLP-1 receptor agonist liraglutide to insulin can reverse insulin-associated weight gain, improve HbA1c and decrease the need for insulin, but is expensive. From a cost perspective, such treatment should be discontinued when it is clear that treatment targets will not be achieved. Our aim was to find the best cost-controlling treatment strategy: the shortest possible trial period needed to discriminate successfully treated patients from those failing to achieve predefined targets of treatment success. METHODS: We used data from the 'Effect of Liraglutide on insulin-associated wEight GAiN in patients with Type 2 diabetes' (ELEGANT) trial, comparing additional liraglutide (n = 47) and standard insulin therapy (n = 24) during 26 weeks, to calculate the costs associated with different trial periods. Treatment success after 26 weeks was defined by having achieved ≥ 2 of the following: ≥ 4% weight loss, HbA1c ≤ 53 mmol/mol (7%), and/or discontinuation of insulin. RESULTS: The additional direct costs of adding liraglutide for 26 weeks were € 699 per patient, or € 137 per 1 kg weight loss, compared with standard therapy. The best cost-controlling treatment strategy (identifying 21 of 23 responders, treating four non-responders) was to continue treatment in patients showing ≥ 3% weight loss or ≥ 60% decrease in insulin dose at 8 weeks, with a total cost of € 246 for this t rial period, saving € 453 in case of early discontinuation. CONCLUSION: An 8-week trial period of adding liraglutide to insulin in patients with insulin-associated weight gain is an effective cost-controlling treatment strategy if the liraglutide is discontinued in patients not showing an early response regarding weight loss or insulin reduction.

Individual and partner's level of occupation and the association with HbA1c levels in people with Type 2 diabetes mellitus: the Dutch Diabetes Pearl cohort.

AIMS: Individual indicators of socio-economic status have been associated with glycaemic control in people with Type 2 diabetes, but little is known about the association between partner's socio-economic status and HbA1c levels. We therefore examined the cross-sectional association between individual and partner's level of occupation on HbA1c levels in people with Type 2 diabetes in the Netherlands. METHODS: We included people with Type 2 diabetes with a partner who were treated in primary, secondary and tertiary care in the Diabetes Pearl cohort. Occupational level was classified according to International Standard Classification of Occupations (ISCO)-08 skill levels. Linear regression analyses were performed stratified for sex, and corrected for age, recruitment centre and diabetes medication. RESULTS: In total, 3257 participants (59.8% men, mean 62.2±9.4 years) were included. For men, having a partner with an intermediate level of occupation was associated with lower HbA1c levels [e.g. ISCO level 3: -2 mmol/mol (95% CI -4;-1) or -0.2% (95% CI -0.4;-0.1)], compared with having a partner of the highest occupational level (ISCO level 4). In women, having an unemployed partner was associated with higher HbA1c levels [14 mmol/mol (95% CI 6; 22) or 1.3% (95% CI 0.6; 2.0)], compared with having a partner of the highest occupational level. CONCLUSIONS: Partner's occupational status provided additional information on the association between socio-economic status and HbA1c levels in people with Type 2 diabetes. Women seemed to benefit from a partner with a higher occupational status, while men seemed to benefit from a partner with a lower status. Because of the cross-sectional nature of the present study, more research is necessary to explore this association.

Impact of a multifaceted strategy to improve perioperative diabetes care.

AIMS: To assess the impact of a multifaceted strategy to improve perioperative diabetes care throughout the hospital care pathway. METHODS: We conducted a controlled before-and-after study in six hospitals. The purpose of the strategy was to target four predominant barriers that obstruct optimal care delivery. We provided feedback on baseline indicator performance, developed a multidisciplinary protocol and patient information, and provided professional education. After a 6-month intervention, we determined the performance changes against three outcome indicators and nine process indicators using data on 811 patients with diabetes who underwent major surgery. The progress of the interventions was monitored closely. RESULTS: Two process indicators improved significantly in the intervention hospitals: the proportion of patients for whom glycaemic control had been evaluated preoperatively increased by 9% (P < 0.002) and the proportion of patients with blood glucose measurements within 1 h after surgery increased by 29% (P < 0.0001). Four other process indicators and all three outcome indicators improved more in the intervention hospitals than in the control hospitals, but the differences were not statistically significant. These included the proportion of patients with all glucose values at 6-10 mmol/l (+3%) and the proportion of patients with hyperglycaemia (-8%). The implementation of the multidisciplinary protocol was still ongoing after the 6-month intervention period. CONCLUSIONS: The multifaceted improvement strategy had a limited impact on the quality of perioperative diabetes care. This study demonstrates the complexity of improving perioperative diabetes care throughout the multiprofessional hospital care pathway.

A comparison of the pharmacodynamic profiles of jet-injected regular human insulin versus conventionally administered insulin aspart in healthy volunteers.

AIMS: Rapid-acting insulin analogues are generally preferred over regular human insulin because of their more immediate onset of action and shorter time-action profile. However, these analogues may not always be tolerated by or universally available for people with insulin-requiring diabetes. Jet injection has been demonstrated to facilitate faster insulin absorption. We determined whether administration of regular human insulin by jet injection achieves the same pharmacological properties as that of a rapid-acting insulin analogue. METHODS: Twenty healthy volunteers received regular human insulin (0.2units/kg) by jet injection. Glucose 20% was infused intravenously to maintain euglycaemia over six hours. The glucose infusion rates (GIR) were determined to compare pharmacological profiles. These profiles were compared with data from two other studies in which a similar dose of insulin aspart was administered by conventional pen. RESULTS: Regular human insulin by jet injection had a faster onset of glucose-lowering effect compared to aspart by conventional pen (T-GIR50%, 30.8±2.9 versus 43.1±3.2min, P<0.01). There were no differences in time to maximal GIR (106.1±11.9 versus 95.8±9.2min, P=0.50), maximal GIR (8.6±0.7 versus 7.7±0.7mg/kg/min, P=0.0.33), total glucose-lowering effect (101.0±9.8 versus 87.6±7.0g, P=0.28), and time until 50% of glucose disposal (144.8±5.6 versus 151.3±5.1min, P=0.39). CONCLUSIONS: Jet-injected regular human insulin had a pharmacological profile that was essentially not dissimilar from that of aspart insulin administered by conventional pen, and can therefore be used as an alternative for conventionally administered rapid-acting insulin analogues.

Surprisingly few psychological problems and diabetes-related distress in patients with poor glycaemic control.

OBJECTIVE: Poor glycaemic control is an undesirable, but frequently encountered problem in diabetes. Reasons for not achieving optimal glycaemic control are not yet clear. A common belief is that psychological factors contribute importantly. This study compared general psychological problems and diabetes-related distress between patients with persistently poor glycaemic control to patients with optimal glycaemic control. METHODS: Patients from an outpatient clinic with type 1 or type 2 diabetes with a mean HbA1c ≥ 86 mmol/mol (≥ 10%) over two consecutive years (poor-control, n = 32) and those with diabetes and a mean HbA1c ≤ 53 mmol/mol (≤ 7%) over two consecutive years (optimal-control, n = 53) were studied. Clinical characteristics were obtained from the medical records. Psychological characteristics were investigated cross-sectionally using questionnaires. RESULTS: Patients in the poor-control group had a higher BMI compared with the optimal-control group. Self- reported previous anxiety was more prevalent in the poor-control group (34 versus 9%). All other mean test scores and proportions of subjects above cut-off levels were similar in the two groups. CONCLUSIONS: Patients with diabetes and persistently poor glycaemic control have surprisingly few psychological problems and diabetes-related emotional distress. It seems that people with diabetes do not see persistent poor glycaemic control as a problem.

Durable efficacy of liraglutide in patients with type 2 diabetes and pronounced insulin-associated weight gain: 52-week results from the Effect of Liraglutide on insulin-associated wEight GAiN in patients with Type 2 diabetes' (ELEGANT) randomized controlled trial.

BACKGROUND: Pronounced weight gain frequently complicates insulin therapy in patients with type 2 diabetes (T2DM). We have previously reported that addition of liraglutide for 26 weeks can reverse insulin-associated weight gain, decrease insulin dose and improve glycaemic control, as compared with continuation of standard insulin treatment. OBJECTIVES: To investigate whether the beneficial effects of liraglutide are sustained up to 52 weeks and whether similar effects could be obtained when liraglutide is added 6 months later. METHODS: Adult T2DM patients with ≥ 4% weight gain within 16 months of insulin therapy completing the first 26-week trial period of open-label addition of liraglutide 1.8 mg day(-1) (n = 26) versus continuation of standard insulin therapy (n = 24) were all treated with liraglutide for another 26 weeks. Results were analysed according to the intention-to-treat principle. RESULTS: Overall, 24 (92%) and 18 (75%) patients originally assigned to liraglutide and standard therapy, respectively, completed the study. Addition of liraglutide decreased body weight to a similar extend when given in the first 26 weeks (liraglutide group) or second 26 weeks (original standard therapy group): -4.4 vs. -4.3 kg (difference -0.32 kg, 95% confidence interval -2.2 to 1.6 kg; P = 0.74). Similar results were also seen in the two groups with regard to decrease in haemoglobin A1c (HbA1c ) (-0.77 vs. -0.66%; P = 0.23) and insulin dose (-28 vs. -26 U day(-1) ; P = 0.32). In both groups, 22% of patients could discontinue insulin. Continuation of liraglutide until 52 weeks led to sustained effects on body weight, HbA1c and insulin-dose requirements. CONCLUSION: In T2DM patients with pronounced insulin-associated weight gain, addition of liraglutide within 2 years leads to sustained reversal of body weight, improved glycaemic control and decrease in insulin dose. Thus, liraglutide offers a valuable therapeutic option.

Insulin administered by needle-free jet injection corrects marked hyperglycaemia faster in overweight or obese patients with diabetes.

AIMS: To test whether jet injection of insulin resulted in faster correction of marked hyperglycaemia than when insulin is injected by a conventional pen in patients with diabetes. METHODS: Adult, overweight or obese (BMI ≥25 and ≤40 kg/m(2)) patients with type 1 diabetes (n = 10) or insulin-treated type 2 diabetes (n = 10) were enrolled in a randomized, controlled, crossover study. On two separate occasions, patients were instructed to reduce insulin dose(s) to achieve marked hyperglycaemia (18-23 mmol/l). Subsequently, insulin aspart was administered either by jet injection or by conventional pen, in a dose based on estimated individual insulin sensitivity. Pharmacodynamic and pharmacokinetic profiles were derived from plasma glucose and insulin levels, measured for 6 h after injection. RESULTS: After conventional injection, plasma glucose concentration dropped by ≥10 mmol/l after 192.5 ± 13.6 min. The jet injector advanced this time to 147.9 ± 14.4 min [difference 44.6 (95% confidence interval 4.3, 84.8); P = 0.03], except in 3 patients who failed to reach this endpoint. The time advantage exceeded 1.5 h in patients with a BMI above the median. Jet injection also reduced the hyperglycaemic burden during the first 2 h (2042 ± 37.2 vs 2168 ± 26.1 mmol/min; P = 0.01) and the time to peak insulin levels (40.5 ± 3.2 vs 76.8 ± 7.7 min; P < 0.001), but did not increase the risk for hypoglycaemia. CONCLUSIONS: Administration of rapid-acting insulin by jet injection results in faster correction of marked hyperglycaemia in overweight or obese patients with insulin-requiring diabetes.

Perioperative diabetes care: room for improving the person centredness.

AIMS: Person centredness is an important principle for delivering high-quality diabetes care. In this study, we assess the level of person centredness of current perioperative diabetes care. METHODS: We conducted a survey in six Dutch hospitals, among 690 participants with diabetes who underwent major abdominal, cardiac or large-joint orthopaedic surgery. The survey included questions regarding seven dimensions of person-centred perioperative diabetes care. RESULTS: Complete data were obtained from 298 participants. The survey scores were low for many of the dimensions of person centredness. The dimensions 'information', 'patient involvement' and 'coordination and integration of care' had the lowest scores. Only half the participants had received information about perioperative diabetes treatment, and approximately one-third had received information about the effect of surgery on blood glucose values, target glucose values and glucose measurement times. Similarly, half the participants had an opportunity to ask questions preoperatively, and only one-third of the participants felt involved in the decision-making regarding diabetes treatment. Most participants knew neither the caregiver in charge of perioperative diabetes treatment nor whom to contact in case of diabetes-related problems during their hospital stay. CONCLUSIONS: Current perioperative diabetes care is characterized by a lack of patient information and limited patient involvement. These results indicate that there is ample room for improving the person centredness of perioperative diabetes care.

Beta2-adrenoceptor stimulation has no effect on skeletal muscle glucose uptake.

INTRODUCTION: Blockade of the ß-adrenergic receptor induces insulin resistance and chronic ß-adrenoceptor stimulation improves insulin sensitivity in animals. We tested whether acute ß2-adrenoceptor stimulation increased insulin-induced glucose uptake in human forearm skeletal muscle. MATERIALS AND METHODS: During a hyperinsulinemic euglycemic clamp procedure, forearm glucose uptake was calculated by multiplying the arteriovenous glucose gradient and forearm blood flow before and during local infusion of the ß2-adrenoceptor salbutamol into the brachial artery. CONCLUSIONS: ß2-Adrenergic stimulation had no effect on insulin-stimulated glucose uptake in human forearm skeletal muscle.

The interleukin-1 receptor antagonist anakinra improves first-phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance.

Inflammation at the level of the ß cell appears to be involved in progressive ß-cell dysfunction in type 2 diabetes. We assessed the effect of blocking interleukin-1 (IL-1) by anakinra [recombinant human interleukin-1 receptor antagonist (IL-1Ra)] on ß-cell function. Sixteen participants with impaired glucose tolerance were treated with 150 mg anakinra daily for 4 weeks in a double blind, randomized, placebo-controlled cross-over study with a wash-out period of 4 weeks. At the end of each treatment period, oral glucose tolerance tests (OGTTs) and hyperglycaemic clamps were performed. First-phase insulin secretion improved after anakinra treatment compared with placebo, 148 ± 20 versus 123 ± 14 mU/l, respectively (p = 0.03), and the insulinogenic index was higher after anakinra treatment. These results support the concept of involvement of IL-1ß in the (progressive) decrease of insulin secretion capacity associated with type 2 diabetes.

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.

Physical fitness can partly explain the metabolically healthy obese phenotype in women.

To investigate whether physical fitness and/or fat distribution and inflammation profile may explain why approximately 30% of the women with obesity are protected against obesity-related disorders.10 metabolically healthy obese women and 10 age- and weight-matched women with the metabolic syndrome were enrolled. Physical fitness (VO2max), daily physical activity levels (METs, steps per day), insulin sensitivity (clamp), body fat distribution (DXA scan) and, inflammation markers and adipokines were determined.The metabolically healthy obese women had a 17% higher VO2max (25.1±3.9 vs. 21.5±3.1 ml ∙ min-1 ∙ kg-1, p=0.04) and tended to take more steps per day (7 388±1 440 vs. 5 927±1 301, p=0.06) than women with the metabolic syndrome. Despite equivalent levels of fat mass, metabolically healthy obese women had significantly lower circulating TNF-α levels compared to women with the metabolic syndrome (3.55±3.83 vs. 0.43±0.97 ng/ml, p=0.03). No differences were seen in insulin sensitivity, adipokines, and inflammatory markers between both groups.Metabolically healthy obese women have a higher cardio-respiratory fitness and lower TNF-α levels, which may partly explain why these women are protected from the detrimental effects of obesity compared to obese women with the metabolic syndrome.

The dipeptidyl peptidase-4 inhibitor vildagliptin does not affect ex vivo cytokine response and lymphocyte function in patients with type 2 diabetes mellitus.

AIMS: The enzyme dipeptidyl peptidase-4 (DPP-4) is a key player in the degradation of incretin hormones that are involved in glucose metabolism. DPP-4 is also expressed on immune cells and is associated with several immunological functions. Some studies have reported increased rates of infections in patients treated with DPP-4 inhibitors. We therefore assessed whether treatment with the DPP-4 inhibitor vildagliptin affected cytokine production and T-cell differentiation. METHODS: Patients with type 2 diabetes were treated with vildagliptin or an active comparator, acarbose, for four weeks, in a randomized cross-over trial. Blood was sampled at the end of each treatment period and peripheral blood mononuclear cells were isolated and stimulated with a broad spectrum of pattern recognition receptor agonists. RESULTS: Serum cytokine concentrations and ex vivo cytokine production (both monocyte and T-cell derived) did not differ during treatment with vildagliptin compared to acarbose. Similarly, ex vivo relative upregulation of mRNA transcription of T-cell lineage specific transcription factors was unaffected by vildagliptin treatment. CONCLUSIONS: These data show that a four-week treatment with vildagliptin in patients with type 2 diabetes mellitus does not result in a significant modulation of cytokine responses. This observation suggests that inhibition of DDP-4 does not lead to an increased risk of infection by diminishing cytokine production.