Trajectories of BMI before and after diagnosis of type 2 diabetes in a real-world population

Aims/hypothesis: Few studies have examined the clinical characteristics associated with changes in weight before and after diagnosis of type 2 diabetes. Using a large real-world cohort, we derived trajectories of BMI pre- and post-diabetes diagnosis and examined the clinical characteristics associated with these trajectories, including assessing the impact of pre-diagnosis weight change on post-diagnosis weight change.Methods: We performed an observational cohort study using electronic medical records from individuals in the Scottish Care Information Diabetes Collaboration database. Two trajectories were calculated based on observed BMI measurements between three years and six months pre-diagnosis, and between one- and five-years post-diagnosis. In the post-diagnosis trajectory, each BMI measurement was time-dependently adjusted for the effects of diabetes medications and HbA1c change.Results: A total of 2736 individuals were included in the study. There was a pattern of pre-diagnosis weight gain with 1944(71%) individuals gaining weight overall, and 875(32%) gaining more than 0.5kg/m2 per year. This was followed by a pattern of weight loss post-diagnosis, with 1722(63%) individuals losing weight. Younger age and greater social deprivation were associated with increased weight gain pre-diagnosis. Pre-diagnosis weight change was unrelated to post-diagnosis weight change, where post-diagnosis weight loss was associated with older age, female sex, higher BMI, higher HbA1c and weight gain during the peri-diagnosis period. Considering the peri-diagnostic period (defined as 6 months prior to 12 months post diagnosis), we identified 986(36%) individuals who had a high HbA1c at diagnosis but who lost weight rapidly and were most aggressively treated at one year; this subgroup had the best glycaemic control at five years.Conclusions/interpretation: Average weight increases before diagnosis and decreases after diagnosis, however, there were significant differences across the population. Younger individuals gain weight pre-diagnosis, but in older individuals type 2 diabetes is less associated with weight gain, consistent with other drivers for diabetes aetiology in the elderly. We have identified a substantial group of individuals who have a rapid deterioration in glycaemic control and weight loss around the time of diagnosis who subsequently stabilise suggesting that a high HbA1c at diagnosis is not inevitably associated with a poor outcome and may be driven by reversible glucose toxicity

A randomised controlled study of high intensity exercise as a dishabituating stimulus to improve hypoglycaemia awareness in people with type 1 diabetes:a proof of concept study

Aims/hypothesis Approximately 25% of people with type 1 diabetes have suppressed counterregulatory hormonal and symptomatic responses to insulin-induced hypoglycaemia, which renders them at increased risk of severe, disabling hypoglycaemia. This is called impaired awareness of hypoglycaemia (IAH), the cause of which is unknown. We recently proposed that IAH develops through habituation, a form of adaptive memory to preceding hypoglycaemia. Consistent with this hypothesis, we demonstrated restoration of defective counterregulatory hormonal responses to hypoglycaemia (referred to as dishabituation) in a rodent model of IAH following introduction of a novel stress stimulus (high intensity training [HIT]). In this proof-of-concept study we sought to further test this hypothesis by examining whether a single episode of HIT would amplify counterregulatory responses to subsequent hypoglycaemia in people with type 1 diabetes who had IAH (assessed by Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating (DAFNE) hypoglycaemia awareness rating 2 or 3). The primary outcome was the difference in adrenaline response to hypoglycaemia following both a single episode of HIT and rest. Methods In this randomised, crossover study 12 participants aged between 18 and 55 years with type 1 diabetes for ≥5 years and an HbA1c < 75 mmol/mol (9%) were recruited. Individuals were randomised using computer generated block randomisation to start with one episode of HIT (4 × 30 s cycle sprints [2 min recovery] at 150% of maximum wattage achieved during V˙O2peak assessment) or rest (control). The following day they underwent a 90 min hyperinsulinaemic–hypoglycaemic clamp study at 2.5 mmol/l with measurement of hormonal counterregulatory response, symptom scores and cognitive testing (four-choice reaction time and digit symbol substitution test). Each intervention and subsequent clamp study was separated by at least 2 weeks. The participants and investigators were not blinded to the intervention or measurements during the study. The investigators were blinded to the primary outcome and blood analysis results. Results All participants (six male and six female, age 19–54 years, median [IQR] duration of type 1 diabetes 24.5 [17.3–29.0] years, mean [SEM] HbA1c 56 [3.67] mmol/mol; 7.3% [0.34%]) completed the study (both interventions and two clamps). In comparison with the rest study, a single episode of HIT led to a 29% increase in the adrenaline (epinephrine) response (mean [SEM]) (2286.5 [343.1] vs 2953.8 [384.9] pmol/l); a significant increase in total symptom scores (Edinburgh Hypoglycaemia Symptom Scale: 24.25 [2.960 vs 27.5 [3.9]; p < 0.05), and a significant prolongation of four-choice reaction time (591.8 [22.5] vs 659.9 [39.86] ms; p < 0.01] during equivalent hypoglycaemia induced the following day. Conclusions/interpretation These findings are consistent with the hypothesis that IAH develops in people with type 1 diabetes as a habituated response and that introduction of a novel stressor can restore, at least partially, the adapted counterregulatory hormonal, symptomatic and cognitive responses to hypoglycaemia.Output Status: Forthcoming/Available Onlin

Body Mass Index's influence on arterial hypertension in Type 1 diabetes - A brief report from IMI-SOPHIA study

Information on BMI and risk of developing hypertension in type 1 diabetes (T1D) is scarce, and it comes mostly from cross-sectional analyses. This study underscores a risk of developing hypertension in T1D individuals with high BMI, and this risk appears to be higher than in those with type 2 diabetes.</p

Body Mass Index's influence on arterial hypertension in Type 1 diabetes - A brief report from IMI-SOPHIA study

Information on BMI and risk of developing hypertension in type 1 diabetes (T1D) is scarce, and it comes mostly from cross-sectional analyses. This study underscores a risk of developing hypertension in T1D individuals with high BMI, and this risk appears to be higher than in those with type 2 diabetes.</p

Dapagliflozin, Inflammation and Left Ventricular Remodelling in Patients with Type 2 Diabetes and Left Ventricular Hypertrophy

Background and AimsSodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data. The aim of our study was to investigate whether improvements in cardiac remodelling caused by dapagliflozin in individuals with type 2 diabetes (T2D) and left ventricular hypertrophy (LVH) were associated with its effects on inflammation.MethodsWe measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation.ResultsFollowing 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p=0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r=0.311), IL-1β (r=0.246), TNF-α (r=0.230)) at 12 months.ConclusionsDapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1β and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin

Cost-Effectiveness of iGlarLixi Versus Premix BIAsp 30 in Patients with Type 2 Diabetes Suboptimally Controlled by Basal Insulin in the UK

INTRODUCTION iGlarLixi is indicated as an adjunct to diet and exercise in addition to metformin (with or without sodium-glucose cotransporter-2 inhibitors) to improve glycemic control in adults with insufficiently controlled type 2 diabetes (T2D). A cost-effectiveness analysis was conducted to compare iGlarLixi with premix biphasic insulin aspart 30 (BIAsp 30) in people with T2D suboptimally controlled with basal insulin (BI). METHODS The IQVIA CORE Diabetes Model was used to estimate lifetime costs and outcomes for people with T2D from a UK health care perspective at a willingness-to-pay threshold of £20,000. Initial clinical data were based on the phase 3 randomized, open-label, active-controlled SoliMix clinical trial which compared the efficacy and safety of once-daily iGlarLixi with that of twice-daily BIAsp 30. Costs associated with management and complications and utilities values were derived from published sources. Lifetime costs (in £GBP) and quality-adjusted life-years (QALYs) were predicted; extensive scenario and sensitivity analyses were conducted. RESULTS Estimated QALYs gained were slightly higher with iGlarLixi (8.9 vs. 8.8) compared with premix BIAsp 30, at a higher cost (£23,204 vs. £21,961). The base case incremental cost-effectiveness ratio (ICER) per QALY was £13,598. Treatment acquisition was the main driver of cost differences (iGlarLixi, £11,750; premix BIAsp 30, £10,395). Costs associated with management and complications were generally similar between comparators. CONCLUSION iGlarLixi provides improved QALY outcomes at an acceptable cost compared with premix BIAsp 30, with an ICER below the threshold generally considered acceptable by UK authorities. In people with T2D, iGlarLixi is a simple, cost-effective option for advancing therapy of BI, with fewer daily injections than premix BIAsp 30

High intensity exercise as a dishabituating stimulus restores counterregulatory responses in recurrently hypoglycemic rodents

Hypoglycemia is a major adverse effect of insulin therapy for people with type 1 diabetes (T1D). Profound defects in the normal counterregulatory response to hypoglycemia explain the frequency of hypoglycemia occurrence in T1D. Defective counterregulation results to a large extent from prior exposure to hypoglycemia per se, leading to a condition called impaired awareness of hypoglycemia (IAH), the cause of which is unknown. In the current study, we investigate the hypothesis that IAH develops through a special type of adaptive memory referred to as habituation. To test this hypothesis, we used a novel intense stimulus (high-intensity exercise) to demonstrate two classic features of a habituated response, namely dishabituation and response recovery. We demonstrate that after recurrent hypoglycemia the introduction of a novel dishabituating stimulus (a single burst of high-intensity exercise) in male Sprague-Dawley rats restores the defective hypoglycemia counterregulatory response. In addition, the rats showed an enhanced response to the novel stimulus (response recovery). We make the further observation using proteomic analysis of hypothalamic extracts that high-intensity exercise in recurrently hypoglycemic rats increases levels of a number of proteins linked with brain-derived neurotrophic factor signaling. These findings may lead to novel therapeutic approaches for individuals with T1D and IAH.</jats:p