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. 2022 Oct;38(7):e3558.
doi: 10.1002/dmrr.3558. Epub 2022 Jul 5.

Insulin resistance and beta-cell dysfunction in newly diagnosed type 2 diabetes: Expression, aggregation and predominance. Verona Newly Diagnosed Type 2 Diabetes Study 10

Enzo Bonora  1 , Maddalena Trombetta  1 , Marco Dauriz  1 , Corinna Brangani  1 , Vittorio Cacciatori  1 , Carlo Negri  1 , Isabella Pichiri  1 , Vincenzo Stoico  1 , Elisabetta Rinaldi  1 , Giuliana Da Prato  1 , Maria Linda Boselli  1 , Lorenza Santi  1 , Federica Moschetta  1 , Monica Zardini  1 , Riccardo C Bonadonna  2
Affiliations

Insulin resistance and beta-cell dysfunction in newly diagnosed type 2 diabetes: Expression, aggregation and predominance. Verona Newly Diagnosed Type 2 Diabetes Study 10

Enzo Bonora et al. Diabetes Metab Res Rev. 2022 Oct.

Abstract

Aims: We investigated quantitative expression, mutual aggregation and relation with hyperglycemia of insulin resistance (IR) and beta-cell dysfunction (BCD) in newly diagnosed type 2 diabetes.

Methods: We assessed IR with euglycemic hyperinsulinemic clamp and BCD with modelled glucose/C-peptide response to oral glucose in 729 mostly drug-naïve patients. We measured glycated hemoglobin, pre-prandial, post-prandial and meal-related excursion of blood glucose.

Results: IR was found in 87.8% [95% confidence intervals 85.4-90.2] and BCD in 90.0% [87.8-92.2] of subjects, ranging from mild to moderate or severe. Approximately 20% of subjects had solely one defect: BCD 10.8% [8.6-13.1] or IR 8.6% [6.6-10.7]. Insulin resistance and BCD aggregated in most subjects (79.1% [76.2-82.1]). We arbitrarily set nine possible combinations of mild, moderate or severe IR and mild, moderate or severe BCD, finding that each had a similar frequency (∼10%). In multiple regression analyses parameters of glucose control were related more strongly with BCD than with IR.

Conclusions: In newly-diagnosed type 2 diabetes, IR and BCD are very common with a wide range of expression but no specific pattern of aggregation. Beta-cell dysfunction is likely to play a greater quantitative role than IR in causing/sustaining hyperglycemia in newly-diagnosed type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01526720.

Keywords: beta-cell dysfunction; hyperglycemia; insulin resistance; newly diagnosed; type 2 diabetes mellitus.

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Conflict of interest statement

None of the authors has anything to disclose which is pertinent to this paper.

Figures

FIGURE 1
FIGURE 1
Frequency of patients with type 2 diabetes with the presence of insulin resistance (IR) and/or beta‐cell defect (beta‐cell dysfunction (BCD)), consisting of a deficit of derivative control (DC) and/or proportional control (PC) of insulin secretion. 95% confidence intervals (CI) are in brackets
FIGURE 2
FIGURE 2
Median of M‐clamp values (μmol/min/m2 Body Surface Area [BSA]; upper panel) and proportional control (PC) values (pmol/m2 BSA/(mmol/l/min; lower panel) after stratification into deciles
FIGURE 3
FIGURE 3
Frequency of combination of a mild (+), moderate (++) or severe (+++) insulin resistance (IR) and deficit of derivative control (DC; upper panel) or proportional control (PC; lower panel) of insulin secretion in patients with newly diagnosed type 2 diabetes
See this image and copyright information in PMC

References

    1. DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773‐795. 10.2337/db09-9028 - DOI - PMC - PubMed
    1. International Diabetes Federation I, IDF Diabetes Atlas. 8th ed. International Diabetes Federation; 2017.
    1. Bonetti S, Trombetta M, Malerba G, et al. Variants and haplotypes of TCF7L2 are associated with β‐cell function in patients with newly diagnosed type 2 diabetes: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 1. J Clin Endocrinol Metab. 2011;96:E389‐E393. 10.1210/jc.2010-1677 - DOI - PubMed
    1. Bonetti S, Trombetta M, Boselli ML, et al. Variants of GCKR affect both β‐cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2. Diabetes Care. 2011;34:1205‐1210. 10.2337/dc10-2218 - DOI - PMC - PubMed
    1. Trombetta M, Bonetti S, Boselli M, et al. CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. the Verona newly diagnosed type 2 diabetes study (VNDS) 3. PLoS ONE. 2012;7:e32755. 10.1371/journal.pone.0032755 - DOI - PMC - PubMed

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