Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes

Abstract

OBJECTIVE Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D. RESEARCH DESIGN AND METHODS In this cross-sectional cohort comprising 489 individuals (64% female, age 41.0 ± 14.0 years), T1D duration was 15.0 (interquartile range [IQR] 6.0–29.0) years. Individuals had a time in range (TIR) of 66% (IQR 52–80%) and a urinary C-peptide-to-creatinine ratio (UCPCR) of 0.01 (IQR 0.00–0.41) nmol/mmol. To assess β-cell function, we measured UCPCR (detectable >0.01 nmol/mmol), and to assess α-cell function, fasting plasma glucagon/glucose ratios were measured. CGM was used to record TIR (3.9–10 mmol/L), time below range (TBR) (<3.9 mmol/L), time above range (TAR) (>10 mmol/L), and glucose coefficient of variance (CV). For CGM, 74.7% used FreeStyle Libre 2, 13.8% Medtronic Guardian, and 11.5% Dexcom G6 as their device. RESULTS The percentage of patients with T1D who had a detectable UCPCR was 49.4%. A higher UCPCR correlated with higher TIR (r = 0.330, P < 0.05), lower TBR (r = −0.237, P < 0.05), lower TAR (r = −0.302, P < 0.05), and lower glucose CV (r = −0.356, P < 0.05). A higher UCPCR correlated negatively with HbA1c levels (r = −0.183, P < 0.05) and total daily insulin dose (r = −0.183, P < 0.05). Glucagon/glucose ratios correlated with longer TIR (r = 0.234, P < 0.05). CONCLUSIONS Significantly longer TIR, shorter TBR and TAR, and lower CV were observed in individuals with greater UCPCR-assessed β-cell function. Therefore, better CGM-derived metrics in individuals with preserved β-cell function may be a contributor to a lower risk of developing long-term complications.

Associations between diabetes-related genetic risk scores and residual beta cell function in type 1 diabetes: the GUTDM1 study

“…Combining our results with those of the above-listed studies, it appears that residual beta cell function is moderately associated with (parts of) the risk for development of type 1 diabetes. Indeed, high GRS-1 and GRS-2 are both associated with lower C-peptide levels, and this association appears to show a strong inverse correlation with age of onset, while adult age of onset is specifically associated with more residual C-peptide production [12]. We therefore hypothesise that people with a higher GRS-1 and GRS-2 have a higher chance of more aggressive disease and therefore lower residual beta cell function.…”

“…Five hundred individuals participated in the GUTDM1 cohort, with data collected from November 2020 to October 2022. The GUTDM1 cohort is a cross-sectional study in the Netherlands designed to investigate the interplay between genetic and environmental factors in the maintenance of residual beta cell function in type 1 diabetes [12]. Participant recruitment and informed consent procedures adhered to the Declaration of Helsinki, and received approval from the local Medical Ethics Committee of the Amsterdam University Medical Centre.…”

“…Methods for DNA isolation, genotyping and quality control, determining genetic ancestry and imputation are described in ESM Methods [12,[31][32][33]. We calculated five GRS based on known associations with incident type 1 diabetes (GRS-1 and GRS-2), type 2 diabetes (GRS-T2D) and C-peptide secretion levels (GRS-C1 and GRS-C2).…”

“…Recently, it has become apparent that a large proportion of individuals with type 1 diabetes have residual beta cell function [10,11], and that this is associated with fewer hypoglycaemic events and long-term complications, and better daily glycaemic control [12][13][14]. New therapeutic strategies such as treatment with verapamil, teplizumab, pleconaril or ribavirin or faecal transplantations have attempted to preserve residual beta cell function [15][16][17].…”

Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats

“…Numerous studies emphasize the protective role of residual beta-cell function against the progression of diabetic complications, highlighting the significant value of treatments capable of sustaining beta-cell mass and function over time [ 24 ]. In the present study, we demonstrated that supplementation of diabetic animals with a promising flavonoid-rich functional food (CCB) significantly reduced pancreatic oxidative stress and inflammation, effectively preventing beta-cell loss and supporting better glycemic control.…”