Beta cell stress in a 4‐year follow‐up of patients with type 2 diabetes: A longitudinal analysis of the <i>BetaDecline</i> Study

Russo, Giuseppina T.; Giorda, Carlo; Cercone, Stefania; Cosmo, Salvatore De; Nicolucci, Antonio; Cucinotta, Domenico

doi:10.1002/dmrr.3016

Cited by 12 publications

(12 citation statements)

References 74 publications

(89 reference statements)

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“…From the 61 included articles, 56 studies assessed the phenotypic factors affecting diabetes progression, while only four studies investigated genotypic determinants of diabetes progression and one study assessed both phenotypic and genotypic factors . Before 2000, there were only four studies published and between 2000 and 2010; there were 20 studies published, with the remaining 37 studies published after 2010.…”

Section: Resultsmentioning

confidence: 99%

“…Before 2000, there were only four studies published and between 2000 and 2010; there were 20 studies published, with the remaining 37 studies published after 2010. The 61 studies were comprised of 35 retrospective cohort studies, 19 prospective cohort studies, three cross‐sectional studies, three case‐control studies studies and one randomized controlled trial (RCT) . The sample size ranged from 50 to 366 955 individuals, and most of the studies were from developed countries with European, American and Australian populations.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty‐six studies (20 retrospective cohort studies, five prospective cohort studies and one RCT) reported HbA1c or fasting blood glucose at diagnosis as one of the main determinants of diabetes progression.…”

Section: Resultsmentioning

confidence: 99%

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The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus

Nair

Donnelly

Dawed

et al. 2020

Endocrino Diabet & Metabol

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Aim:To conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression. Methods:We conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined.Results: Our search yielded 2785 articles; based on title, abstract and full-text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: 'Initiation of insulin', 'Initiation of oral antidiabetic drug', 'treatment intensification', 'antidiabetic therapy failure', 'glycaemic deterioration', 'decline in betacell function' and 'change in insulin dose'. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi-ethnic studies. Conclusion:We have identified the major determinants of diabetes progressionyounger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large-scale studies of diabetes progression in different ethnic groups. K E Y W O R D S diabetes progression, glycaemic deterioration, insulin initiation, type 2 diabetes S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Thakarakkattil Narayanan Nair A, Donnelly LA, Dawed AY, et al. The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus. Endocrinol Diab Metab. 2020;3:e00108.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus

Nair

Donnelly

Dawed

et al. 2020

Endocrino Diabet & Metabol

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“…Pancreatic β cell failure, characterized by progressive decline in glucose‐stimulated insulin secretion and loss of viable β cells, is critical to the development of type 2 diabetes . It is driven by β cell “overstimulation” and subsequent “exhaustion” in response to insulin resistance and glucolipotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Pancreatic β cell failure, characterized by progressive decline in glucose-stimulated insulin secretion and loss of viable β cells, is critical to the development of type 2 diabetes. 38,39 It is driven by β cell "overstimulation" and subsequent "exhaustion" in response to insulin resistance and glucolipotoxicity. Thus, alleviating insulin demand on β cells provides β cell rest, which would replenish insulin secretory capacity to rescue "exhausted" β cell and preserve long-term β cell function.…”

Section: Discussionmentioning

confidence: 99%

Improved skeletal muscle energy metabolism relates to the recovery of β cell function by intensive insulin therapy in drug naïve type 2 diabetes

Tang

Zhang

Wang

et al. 2019

Diabetes Metabolism Res

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Aims Diminished energy turnover of skeletal muscle is involved in the development of type 2 diabetes. Intensive insulin therapy has been reported to maintain glycaemic control in newly diagnosed type 2 diabetes, while the underlying mechanism remains unclear. Herein, we aimed to characterize the contribution of muscular mitochondrial oxidative phosphorylation (OxPhos) activity to insulin‐induced glycaemic control. Materials and methods There were 21 drug naïve patients with type 2 diabetes receiving continuous subcutaneous insulin infusion for 7 days. Nine nondiabetics matched for age, body mass index, and physical activity were recruited as controls. We applied 31P magnetic resonance spectroscopy to record in vivo muscular phosphocreatine (PCr) flux in controls and diabetics before and after insulin therapy. The mitochondrial OxPhos rate was calculated as ΔPCr / Δtime during the first 50 seconds after cessation of exercise. Results In drug naïve type 2 diabetes, muscular mitochondrial OxPhos rate was restored after insulin therapy. Notably, this alteration was positively associated with the improvements of 1,5‐anhydroglucitol, a serum marker for glucose control over the last 1 week, as well as homeostasis model assessment of β cell function and C‐peptide/glucose ratio t0, two indices for basal insulin secretion. Furthermore, patients with diabetes family history and more severe glucotoxicity tend to achieve greater improvement in mitochondrial function by insulin. Conclusions This study provides evidence that intensive insulin therapy facilitates muscular energy metabolism in drug naïve type 2 diabetes. It correlates to the recovery of β cell function, contributing to insulin‐induced glucose control.

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Different β‐cell secretory phenotype in non‐obese compared to obese early type 2 diabetes

Gudipaty

Rosenfeld

Fuller

et al. 2020

Diabetes Metabolism Res

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Background: Type 2 diabetes (T2D) is characterized by impaired tissue sensitivity to insulin action (ie, insulin resistance) and impaired β-cell insulin secretion. Because obesity contributes importantly to the development of insulin resistance, we sought to determine whether insulin secretory defects would predominate in non-obese compared to obese T2D. Methods:We measured β-cell function and secretory capacity using the glucose-potentiated arginine test in T2D subjects early in the disease course classified as non-obese (BMI <30; n = 12) or obese (BMI ≥30 kg/m 2 ; n = 28) and additionally compared responses from non-obese T2D with a non-diabetic control group (n = 12). Results:The acute insulin response to glucose potentiation of arginine-induced insulin release was less in non-obese T2D than in controls and associated with impaired β-cell sensitivity to glucose (PG 50 ). Proinsulin secretory ratios were increased in nonobese T2D when compared to obese T2D. Obese T2D subjects had reduced insulin sensitivity (M/I) while non-obese T2D subjects had insulin sensitivity that was comparable to controls. Conclusions:In non-obese T2D, insulin secretory defects predominate with impaired β-cell sensitivity to glucose and proinsulin processing in the absence of insulin resistance. Future studies should consider whether different β-cell secretory phenotypes and tissue sensitivity to insulin explain the varying responsiveness to T2D interventions.

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Beta cell stress in a 4‐year follow‐up of patients with type 2 diabetes: A longitudinal analysis of the BetaDecline Study

Abstract: In this cohort of patients with T2DM, beta cell function progressively deteriorated despite current therapies. Among a large set of clinical and biochemical predictors, only baseline HbA1c levels and their deterioration overtime were associated with higher beta cell stress over time.

Cited by 12 publications

References 74 publications

The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus

The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus

Improved skeletal muscle energy metabolism relates to the recovery of β cell function by intensive insulin therapy in drug naïve type 2 diabetes

Different β‐cell secretory phenotype in non‐obese compared to obese early type 2 diabetes

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