IRIS II Study: Intact Proinsulin Is Confirmed as a Highly Specific Indicator for Insulin Resistance in a Large Cross-Sectional Study Design

Pfützner, Andreas; Standl, Eberhard; Hohberg, C.; Konrad, Thomas R.; Strotmann, Hermann-Josef; Lübben, G.; Langenfeld, Matthias; Schulze, Jan; Forst, Thomas

doi:10.1089/dia.2005.7.478

Cited by 28 publications

(33 citation statements)

References 42 publications

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“…A positive relationship between intact proinsulin levels and IR has been suggested in some, but not all, previous studies (6,7,40). Consistent with this, the absolute concentrations of both total and intact proinsulin were positively associated with the HOMA index of IR and negatively related to the Matsuda index of insulin sensitivity.…”

Section: Discussionsupporting

confidence: 81%

“…While in healthy, non-diabetic subjects, these precursors constitute only a minor fraction of the total amount of secreted insulin, the release of proinsulin is significantly increased in patients with type 2 diabetes as well as in individuals with impaired glucose tolerance (IGT) (2)(3)(4)(5). A couple of recent studies have also reported an increase in intact proinsulin levels in insulin-resistant individuals (6,7), although this finding has not been confirmed by others (8,9). Nevertheless, the determination of intact proinsulin as a marker for the diagnosis of insulin resistance (IR) has been widely advocated (10).…”

Section: Introductionmentioning

confidence: 99%

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Proinsulin levels in patients with pancreatic diabetes are associated with functional changes in insulin secretion rather than pancreatic β-cell area

Breuer¹,

Menge²,

Banasch³

et al. 2010

European Journal of Endocrinology

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Introduction: Hyperproinsulinaemia has been reported in patients with type 2 diabetes. It is unclear whether this is due to an intrinsic defect in b-cell function or secondary to the increased demand on the b-cells. We investigated whether hyperproinsulinaemia is also present in patients with secondary diabetes, and whether proinsulin levels are associated with impaired b-cell area or function. Patients and methods: Thirty-three patients with and without diabetes secondary to pancreatic diseases were studied prior to pancreatic surgery. Intact and total proinsulin levels were compared with the pancreatic b-cell area and measures of insulin secretion and action. Results: Fasting concentrations of total and intact proinsulin were similar in patients with normal, impaired (including two cases of impaired fasting glucose) and diabetic glucose tolerance (PZ0.58 and PZ0.98 respectively). There were no differences in the total proinsulin/insulin or intact proinsulin/insulin ratio between the groups (PZ0.23 and PZ0.71 respectively). There was a weak inverse association between the total proinsulin/insulin ratio and pancreatic b-cell area (r

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Proinsulin levels in patients with pancreatic diabetes are associated with functional changes in insulin secretion rather than pancreatic β-cell area

Breuer¹,

Menge²,

Banasch³

et al. 2010

European Journal of Endocrinology

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“…An unfolded protein response could be initiated if such demand exceeds capacity, potentially leading to cell apoptosis (Pfützner et al 2004, Prentki & Nolan 2006. Elevated circulating proinsulin is an indicator for risk of developing diabetes in humans (Wareham et al 1999, Pfützner et al 2005, Prentki & Nolan 2006, Strawbridge et al 2011, von Berghes et al 2011. Proinsulin mutation in Akita mice results in accumulation of misfolded proinsulin that activates ER stressinduced βcell death (Hong et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes

Yang

Gotzmann

Kuny

et al. 2016

Journal of Endocrinology

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We compared the evolution of insulin resistance, hyperglycemia, and pancreatic β-cell dysfunction in the Nile rat (Arvicanthis niloticus), a diurnal rodent model of spontaneous type 2 diabetes (T2D), when maintained on regular laboratory chow versus a high-fiber diet. Chow-fed Nile rats already displayed symptoms characteristic of insulin resistance at 2 months (increased fat/lean mass ratio and hyperinsulinemia). Hyperglycemia was first detected at 6 months, with increased incidence at 12 months. By this age, pancreatic islet structure was disrupted (increased α-cell area), insulin secretion was impaired (reduced insulin secretion and content) in isolated islets, insulin processing was compromised (accumulation of proinsulin and C-peptide inside islets), and endoplasmic reticulum (ER) chaperone protein ERp44 was upregulated in insulin-producing β-cells. By contrast, high-fiber-fed Nile rats had normoglycemia with compensatory increase in β-cell mass resulting in maintained pancreatic function. Fasting glucose levels were predicted by the α/β-cell ratios. Our results show that Nile rats fed chow recapitulate the five stages of progression of T2D as occurs in human disease, including insulinresistant hyperglycemia and pancreatic islet β-cell dysfunction associated with ER stress. Modification of diet alone permits long-term β-cell compensation and prevents T2D. 343-356229:3 β-cell phenotype in type 2 diabetic Nile rats k yang and others

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“…The cross-sectional IRIS study was initially performed to identify diagnostic parameters for insulin resistance in non-insulin-treated patients with type 2 diabetes that are suitable for daily practice (13)(14)(15). Analysis of the same patient population presented here was performed to evaluate the correlation between cardiovascular risk, as identified by hsCRP risk assessment and b-cell dysfunction, and insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Assessment of insulin resistance was performed by analysis of fasting intact proinsulin values or homeostatic model assessment (HOMA IR ) score calculation. Patients with intact proinsulin values exceeding the normal reference value of 11 pmol/L were considered to be insulin-resistant (14,15). In the case of normal intact proinsulin values, HOMA IR score calculation was applied, as previously published (17).…”

Section: Methodsmentioning

confidence: 99%

Association of high-sensitive C-reactive protein with advanced stage β-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus

Pfützner¹,

Standl²,

Strotmann³

et al. 2006

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: Type 2 diabetes mellitus is associated with increased cardiovascular risk. One laboratory marker for cardiovascular risk assessment is highsensitivity C-reactive protein (hsCRP). Methods: This cross-sectional study attempted to analyze the association of hsCRP levels with insulin resistance, b-cell dysfunction and macrovascular disease in 4270 non-insulin-treated patients with type 2 diabetes w2146 male, 2124 female; mean age "SD, 63.9"11.1 years; body mass index (BMI) 30.1"5.5 kg/m

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IRIS II Study: Intact Proinsulin Is Confirmed as a Highly Specific Indicator for Insulin Resistance in a Large Cross-Sectional Study Design

Cited by 28 publications

References 42 publications

Proinsulin levels in patients with pancreatic diabetes are associated with functional changes in insulin secretion rather than pancreatic β-cell area

Proinsulin levels in patients with pancreatic diabetes are associated with functional changes in insulin secretion rather than pancreatic β-cell area

Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes

Association of high-sensitive C-reactive protein with advanced stage β-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus

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