There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of ...established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials.
Data were collected from adults with T2D managed in primary or specialist care in Australia, China, Japan, Czech Republic, France, Hungary, Italy, Argentina, Brazil, Mexico, Israel, Kingdom of Saudi Arabia, and Turkey in 2019, using standardized methodology. CVD prevalence, weighted by diabetes prevalence in each country, was estimated for the overall CAPTURE sample and participating countries. Country-specific odds ratios for CVD prevalence were further adjusted for relevant demographic and clinical parameters.
The overall CAPTURE sample included 9823 adults with T2D (n = 4502 from primary care; n = 5321 from specialist care). The overall CAPTURE sample had median (interquartile range) diabetes duration 10.7 years (5.6-17.9 years) and glycated hemoglobin 7.3% (6.6-8.4%) 56 mmol/mol (49-68 mmol/mol). Overall weighted CVD and atherosclerotic CVD prevalence estimates were 34.8% (95% confidence interval CI 32.7-36.8) and 31.8% (95% CI 29.7-33.8%), respectively. Age, gender, and clinical parameters accounted for some of the between-country variation in CVD prevalence. GLAs with demonstrated cardiovascular benefit were used by 21.9% of participants, which was similar in participants with and without CVD: 21.5% and 22.2%, respectively.
In 2019, approximately one in three adults with T2D in CAPTURE had diagnosed CVD. The low use of GLAs with demonstrated cardiovascular benefit even in participants with established CVD suggested that most were not managed according to contemporary diabetes and cardiology guidelines. Study registration NCT03786406 (registered on December 20, 2018), NCT03811288 (registered on January 18, 2019).
Aims/hypothesis
Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations ...occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants.
Methods
In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine.
Results
Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of
CHGA
did not vary along the intestinal tract, but the mRNA expression of
GCG
,
GIP
,
PYY
,
PCSK1
and
PCSK2
differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of
GCG
and
PYY
was greater in the colon, while the expression of
GIP
and
PCSK1
was greater in the small intestine and colon, and the expression of
PCSK2
was greater in the small intestine.
Conclusions/interpretation
Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants.
Trial registration:
NCT03044860.
Introduction
Liraglutide has demonstrated a significant reduction in the primary major composite cardiovascular (CV) outcome (CV death, non-fatal myocardial infarction, non-fatal stroke). This study ...aimed to determine the cost–utility of adding liraglutide to the standard of care (SoC) for treating type 2 diabetes (T2D) in Thailand for three cohorts: people with atherosclerotic cardiovascular disease (ASCVD), with no ASCVD, and all people with T2D.
Methods
A Markov model was developed to capture the long-term costs and outcomes under the perspective of the healthcare system. Costs were based on local data, the transitional probabilities were derived from the LEADER trial, and utilities were derived from published studies. Future costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed.
Results
Compared to SoC, adding liraglutide incurred higher costs and gained more quality-adjusted life-years (QALYs), yielding incremental cost-effectiveness ratios (ICERs) of above 1 million Thai baht (THB) for the three cohorts. The most influential parameter was the discount rate. When the annual cost of liraglutide reduced from 87,874 to 30,340 THB, 30,116 THB, and 31,617 THB for all people with T2D, people with ASCVD, and people without ASCVD, respectively, the ICER fell below the local threshold of 160,000 THB/QALY. Compared to the SoC treatment, the liraglutide group acquired more clinical benefit in terms of fewer CVD. Sensitivity analyses revealed that with an increase in the level of willingness-to-pay (WTP) threshold, adding liraglutide had an increased chance of being a cost-effective strategy.
Conclusion
Compared to the SoC treatment, adding liraglutide at the current cost is not cost-effective at the local WTP. People with T2D with ASCVD would have the most potential gain from adding liraglutide treatment compared to other populations.
Aims/hypothesis
We studied the impact of Roux-en-Y gastric bypass (RYGB) on the density and hormonal gene expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes.
...Methods
Twelve patients with diabetes and 11 age- and BMI-matched controls underwent RYGB followed by enteroscopy ~10 months later. Mucosal biopsies taken during surgery and enteroscopy were immunohistochemically stained for glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and prohormone convertase 2 (PC2) and the expression of
GCG
(encoding preproglucagon),
PYY
,
CCK
,
GIP
,
GHRL
(encoding ghrelin),
SCT
(encoding secretin),
NTS
(encoding neurotensin) and
NR1H4
(encoding farnesoid X receptor) was evaluated.
Results
The density of cells immunoreactive for GLP-1, CCK and GIP increased in patients after RYGB and the density of those immunoreactive for GLP-1, PYY, CCK and PC2 increased in controls. In both groups,
GHRL
,
SCT
and
GIP
mRNA was reduced after RYGB while
PYY
,
CCK
,
NTS
and
NR1H4
gene expression was unaltered.
GCG
mRNA was upregulated in both groups.
Conclusions/interpretation
Numerous alterations in the distribution of enteroendocrine cells and their expression of hormonal genes are seen after RYGB and include increased density of GLP-1-, PYY-, CCK-, GIP- and PC2-positive cells, reduced gene expression of
GHRL
,
SCT
and
GIP
and increased expression of
GCG
.
•Gut expression of guanylin peptides is elevated in obese patients upon gastric bypass.•Guanylin and uroguanylin show no body weight or glucoregulatory effects in mice.•Uroguanylin has no effect on ...glucose-stimulated insulin secretion in rat pancreas.•Adenoviral gene delivery of uroguanylin is weight-neutral in diet-induced obese rats.•Guanylin peptides do not show promise as novel targets in diabetes and obesity.
To determine whether intestinal expression of guanylate cyclase activator 2A (GUCA2A) and guanylate cyclase activator 2B (GUCA2B) genes is regulated in obese humans following Roux-en-Y gastric bypass (RYGB), and to evaluate the corresponding guanylin (GN) and uroguanylin (UGN) peptides for potentially contributing to the beneficial metabolic effects of RYGB.
Enteroendocrine cells were harvested peri- and post-RYGB, and GUCA2A/GUCA2B mRNA expression was compared. GN, UGN and their prohormones (proGN, proUGN) were administered subcutaneously in normal-weight mice to evaluate effects on food intake and glucose regulation. The effect of pro-UGN or UGN overexpression, using adeno-associated virus (AAV) vectors, was assessed in diet-induced obese (DIO) mice. Intracerebroventricular administration of GN and UGN was performed in rats for assessment of putative centrally mediated effects on food intake. GN and UGN, as well as their prohormones, were evaluated for effects on glucose-stimulated insulin secretion (GSIS) in rat pancreatic islets and perfused rat pancreas.
GUCA2A and GUCA2B mRNA expression was significantly upregulated in enteroendocrine cells after RYGB. Peripheral administration of guanylins or prohormones did not influence food intake, oral glucose tolerance, and GSIS. Central administration of GN and UGN did not affect food intake in rats. Chronic AVV-mediated overexpression of UGN and proUGN had no effect on body weight or glucose homeostasis in DIO mice.
GN and UGN, as well as their prohormones, do not seem to play a significant role in body weight regulation and glycemic control, suggesting that guanylin-family peptides do not show promise as targets for the treatment of obesity or diabetes.
Objective
Our objective was to investigate willingness to pay (WTP) for biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes mellitus (T2DM) in India.
Methods
A multicenter, ...prospective, non-interventional, preference study was conducted that assessed WTP for BIAsp 30 in an insulin pen (FlexPen
®
or Penfill
®
device) in patients in India with T2DM previously treated with biphasic human insulin (BHI) in vials and believed to be able to pay for treatment. The primary endpoint was the proportion of patients willing to continue to pay for BIAsp 30 after 12 weeks’ treatment. Secondary endpoints included the change from baseline in treatment and device satisfaction and patient preferences for treatment attributes as assessed by a nested discrete-choice experiment.
Results
Overall, 54.9% (
n
= 277/505) of participants were male; the mean age was 56.4 years; diabetes duration was 10.9 years; 63.8% had a body mass index ≥ 25 kg/m
2
; > 75% had an annual household income > 150,000 Indian rupees (INR). After 12 weeks’ treatment, 96.4% of patients were willing to pay for BIAsp 30. Mean treatment and device satisfaction significantly improved from baseline (
p
< 0.0001). Patients were willing to pay INR3576 (95% confidence interval CI 2755–4398) for improved glycemic control, INR688 (95% CI 383–994) for a device upgrade (vial/syringe to an insulin pen), or INR327 (95% CI 95–560) to avoid major hypoglycemia. Patients would need to be compensated INR44 (95% CI 56–32) per minor hypoglycemic event.
Conclusions
In India, patients with T2DM previously treated with BHI were willing to pay for BIAsp 30 in an insulin pen. Furthermore, treatment and device satisfaction improved after this therapeutic switch.
Trial Registration
ClinicalTrials.gov: NCT03374774.
Aims
Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to ...effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs).
Materials and methods
An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care.
Results
A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow‐up appointments are required.
Conclusions
Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.
Objective: In both randomized, controlled trials and real-world studies, liraglutide (Victoza®) has demonstrated glycemic and body weight benefits in patients with type 2 diabetes mellitus (T2DM). To ...achieve long-term beneficial outcomes, persistence with treatment is important; however, this can be challenging with injectable drugs. In this study, we examined the association of long-term adherence to liraglutide and metabolic changes.
Methods: A retrospective analysis of patients with T2DM (≥18 years old) from Maccabi Healthcare Services, Israel, who initiated liraglutide from 2010-2015 and had HbA1c measurements at treatment initiation and after 24 months. Mean change in HbA1c and body weight from initiation to 24 months was compared between patients who received liraglutide regularly for at least 12 months (’continuers’) and those who discontinued liraglutide before 12 months (’discontinuers’). Patients who were treated with another GLP-1 receptor agonist, or who underwent bariatric surgery, were excluded. Adjustment for potential confounding factors (sex, age, years in diabetes registry, HbA1c, body mass index, and insulin use at treatment start) was performed using propensity score matching (1:1 n=882 in each group).
Results: Significant reductions in HbA1c were seen in continuers compared with discontinuers (0.80% vs. 0.32%, p<0.0001), despite more using insulin (70.2% vs. 59.0%, p<0.0001) and ≥3 oral antihyperglycemic drugs (20.6% vs. 6.2%, p<0.0001) among discontinuers (in the 3 months preceding the last measurement). Mean body weight reduction was higher in continuers than in discontinuers (3.57 kg vs. 1.25 kg; p<0.0001), but no statistically significant differences were observed in low-density lipoprotein cholesterol (5.72 vs. 2.83 mg/dl p=0.4717) and triglycerides (10.37 vs. 6.89 mg/dl p=0.7896).
Conclusion: In a real-world setting, persistent use of liraglutide was associated with good glycemic and body weight control.
Disclosure
C. Melzer Cohen: None. G. Chodick: None. L.N. Husemoen: Employee; Self; Novo Nordisk A/S. N. Rhee: Employee; Self; Novo Nordisk A/S. V. Shalev: None. A. Karasik: Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S, AstraZeneca. Research Support; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Merck & Co., Inc., GlucoMe.
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