Diabetes Foundation

This study combines live pancreas tissue slices with viral transduction of the Calcium Modulated Photoactivatable Ratiometric Integrator 2 (CaMPARI2) biosensor for high-throughput analysis of islet calcium secretagogue responses. A key challenge of the pancreas slice model has been efficient transgene delivery throughout the slice volume while maintaining viability and function. Here, we demonstrate a robust adenoviral gene delivery approach to transduce slices with CaMPARI2 and apply photoconverting light to permanently mark glucose-induced calcium activity across all islets. This approach demonstrates glucose responsive CaMPARI2 labeling that correlates with insulin secretion. Using this novel high-throughput approach, we examine the relationship between islet size and calcium response. Larger isolated islets exhibit greater CaMPARI2 photoconversion in high glucose, whereas no size-function correlation is observed in islets resident in live slices. We also observe that slices capture a substantially higher proportion of small islets than isolated islets. Integrating CaMPARI2 with live pancreas slice studies enables multiplexed analyses, linking functional readouts to spatial features.

This study combines live pancreas tissue slices with viral transduction of the Calcium Modulated Photoactivatable Ratiometric Integrator 2 (CaMPARI2) biosensor for high-throughput analysis of islet calcium secretagogue responses. A key challenge of the pancreas slice model has been efficient transgene delivery throughout the slice volume while maintaining viability and function. Here, we demonstrate a robust adenoviral gene delivery approach to transduce slices with CaMPARI2 and apply photoconverting light to permanently mark glucose-induced calcium activity across all islets. This approach demonstrates glucose responsive CaMPARI2 labeling that correlates with insulin secretion. Using this novel high-throughput approach, we examine the relationship between islet size and calcium response. Larger isolated islets exhibit greater CaMPARI2 photoconversion in high glucose, whereas no size-function correlation is observed in islets resident in live slices. We also observe that slices capture a substantially higher proportion of small islets than isolated islets. Integrating CaMPARI2 with live pancreas slice studies enables multiplexed analyses, linking functional readouts to spatial features.

Background/Objectives: A stem cell therapy for type 1 diabetes (T1D) is experimentally available but only to those few humans in whom the use of systemic immunosuppression can be justified. For others with T1D, a means to deliver the islets needs to be perfected. We have previously bioengineered a removable device for this purpose and now wish to test the effect of adding extracellular matrix (ECM) derived from decellularised human pancreas to it. Methods: The complete device consists of encapsulated pluripotent stem cell differentiated islets seeded into tubular scaffolds of polycaprolactone made by melt electrospin writing and to which ECM was added. The seeded device was implanted either subcutaneously (SC) or intraperitoneally (IP) into streptozotocin diabetic immunodeficient mice. The outcome over the next few months was compared with that achieved in diabetic mice implanted IP with encapsulated islets alone. Results: The device seeded with encapsulated islets but not containing ECM functioned less well than encapsulated islets implanted alone, with lower human C-peptide production. However, when ECM was added to the seeded device and whether implanted SC or IP, islets functioned as efficiently as those implanted without use of a scaffold. Conclusions: These data provide optimism for the use of seeded scaffolds in diabetic humans in whom a single scaffold seeded with multiple encapsulated islets can more readily be removed if needed for safety reasons than can multiple encapsulated islets not seeded into a scaffold.

Cigarette smoking is a well-established risk factor for diabetes, but the relationship between e-cigarette use and diabetes remains uncertain. Evidence to date has been drawn almost entirely from North America and Asia, with little information from European populations. We conducted a cross-sectional study of 17,854 adults aged 16 years and older from the 2017, 2018, 2019, and 2021 waves of the nationally representative Scottish Health Survey. Diabetes status was based on self-report of doctor-diagnosed diabetes. Participants were classified into six mutually exclusive categories of smoking and e-cigarette use: never users of either cigarettes or e-cigarettes, ex-smokers (former smokers who never used e-cigarettes), current exclusive cigarette smokers, current exclusive e-cigarette users, current dual users, and former e-cigarette users. Weighted prevalence estimates and survey-weighted binary logistic regression models were used to examine associations, adjusting for age group, sex, education, deprivation quintile, ethnicity, alcohol use, physical activity, and hypertension. Diabetes prevalence was highest among ex-smokers (11.3%, 95% CI: 10.1-12.5). Prevalence was 5.7% (95% CI: 5.2-6.2) among never users of either cigarettes or e-cigarettes, 6.2% (95% CI: 4.9-7.9) among current exclusive cigarette smokers, 4.9% (95% CI: 3.4-7.1) among current exclusive e-cigarette users, 8.3% (95% CI: 5.8-11.8) among current dual users, and 5.1% (95% CI: 4.1-6.3) among former e-cigarette users. In adjusted models, ex-smokers had 35% higher odds of diabetes compared with never users of either cigarettes or e-cigarettes (OR=1.35, 95% CI=1.14-1.60, p<0.001), whereas current exclusive smokers (OR=0.78, 95% CI=0.58-1.03, p=0.084), current exclusive e-cigarette users (OR=0.81, 95% CI=0.53-1.22, p=0.309), current dual users (OR=1.49, 95% CI=0.94-2.38, p=0.091), and former e-cigarette users (OR=1.00, 95% CI=0.78-1.29, p=0.973) were not significantly different from never users. Sensitivity analyses restricting ex-smokers to those with ≥5 years since cessation and limiting the sample to adults aged ≥45 years reproduced the same pattern of results. In this nationally representative study of Scottish adults, excess diabetes prevalence was observed among ex-smokers, a pattern that may reflect both reverse causation if individuals quit smoking after diagnosis and the lasting metabolic effects of cumulative smoking exposure. Neither current nor former e-cigarette use was associated with diabetes, and the observed variation in prevalence appeared linked to smoking history rather than e-cigarette use. However, because vaping is relatively recent, further longitudinal research is needed to clarify any long-term risks.

IntroductionPrediabetes is increasing in India and progresses rapidly to type 2 diabetes. The impact of vitamin D3 supplementation on telomerase activity and leukocyte telomere length (LTL) among people with prediabetes has been poorly researched.Research Design and MethodsIn this 18-month prospective trial, we enrolled 121 women with prediabetes and randomized them into intervention (vitamin D3 supplementation, n = 61) and placebo (n = 60) groups. LTL and telomerase activity were measured.ResultsIn the current study, LTL and telomerase activity were assessed at visit 1 (week 0), visit 2 (week 52), and visit 3 (week 78). LTL increased significantly in the intervention group by week 52 (P = .004) and became more pronounced at week 78 (P = .001), representing a 14.5% increase from baseline. Similarly, telomerase activity showed progressive enhancement with vitamin D treatment, achieving significance by week 52 (P = .001) and continuing through week 78 (P < .0001), reflecting a 16.2% increase from baseline. Within-group analysis confirmed significant improvements over time in the vitamin D group (P = .002) but not in placebo (P = .18) group. After adjusting for potential confounders including body mass index, subscapular skinfold thickness, fasting blood glucose, and PTH, serum 25-hydroxyvitamin D levels maintained a significant independent association with both LTL (OR = 2.053; 95% CI, 1.410-2.243; P = .001) and telomerase activity (OR = 2.032; 95% CI, 1.410-2.254; P = .001) in the intervention group.ConclusionVitamin D supplementation, over 78 weeks, is independently associated with increased LTL and telomerase activity in Asian Indian women with prediabetes.

The increasing prevalence of type 2 diabetes mellitus (T2DM) and the associated challenges in treatment are a cause of concern worldwide. Gliclazide is an oral antidiabetes drug used in the treatment of T2DM. It is a second-generation sulphonylurea (SU) which controls blood glucose levels and offers additional benefits. It is distinct from other SUs in terms of its molecular and structural properties. Early aggressive management of blood glucose in diabetes has been shown to provide advantages for micro- and macrovascular complications. Hence, this review is intended to discuss the glycemic and extraglycemic effects of gliclazide.