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

Gudipaty, Lalitha; Rosenfeld, Nora K.; Fuller, Carissa; Cuchel, Marina; Rickels, Michael R.

doi:10.1002/dmrr.3295

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…Emerging evidence indicates that obese (i.e., BMI more than 30 kg/m 2 ) and non-obese people with diabetes have different metabolic profiles. For example, a 2020 clinical study investigating insulin sensitivity (with the use of a hyperinsulinemic-euglycemic clamp) of non-obese versus obese individuals with T2DM demonstrated that insulin sensitivity (determined by the ratio of metabolic rate to steady-state insulin) was more than two-times greater in non-obese than obese individuals with T2DM (p < 0.05) [21]. Another clinical study using a clamp technique to investigate glucose metabolism in non-obese versus obese individuals with T2DM also showed significant differences in insulin sensitivity (i.e., insulin sensitivity index, p < 0.01) and insulin secretion (i.e., fasting C-peptide response, p < 0.05) [22].…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

Skudder-Hill

Cho

et al. 2020

Nutrients

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Both type 2 prediabetes/diabetes (T2DM) and new-onset prediabetes/diabetes after acute pancreatitis (NODAP) are characterized by impaired tissue sensitivity to insulin action. Although the outcomes of NODAP and T2DM are different, it is unknown whether drivers of insulin resistance are different in the two types of diabetes. This study aimed to investigate the associations between abdominal fat phenotypes and indices of insulin sensitivity in non-obese individuals with NODAP, T2DM, and healthy controls. Indices of insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA-IS), Raynaud index, triglyceride and glucose (TyG) index, Matsuda index) were calculated in fasting and postprandial states. Fat phenotypes (intra-pancreatic fat, intra-hepatic fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using magnetic resonance imaging and spectroscopy. Linear regression and relative importance analyses were conducted. Age, sex, and glycated hemoglobin A1c were adjusted for. A total of 78 non-obese individuals (26 NODAP, 20 T2DM, and 32 healthy controls) were included. Intra-pancreatic fat was significantly associated with all the indices of insulin sensitivity in the NODAP group, consistently in both the unadjusted and adjusted models. Intra-pancreatic fat was not significantly associated with any index of insulin sensitivity in the T2DM and healthy controls groups. The variance in HOMA-IS was explained the most by intra-pancreatic fat (R2 = 29%) in the NODAP group and by visceral fat (R2 = 21%) in the T2DM group. The variance in the Raynaud index was explained the most by intra-pancreatic fat (R2 = 18%) in the NODAP group and by visceral fat (R2 = 15%) in the T2DM group. The variance in the TyG index was explained the most by visceral fat in both the NODAP group (R2 = 49%) and in the T2DM group (R2 = 25%). The variance in the Matsuda index was explained the most by intra-pancreatic fat (R2 = 48%) in the NODAP group and by visceral fat (R2 = 38%) in the T2DM group. The differing association between intra-pancreatic fat and insulin resistance can be used to differentiate NODAP from T2DM. Insulin resistance in NODAP appears to be predominantly driven by increased intra-pancreatic fat deposition.

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Section: Introductionmentioning

confidence: 99%

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

Skudder-Hill

Cho

et al. 2020

Nutrients

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“…β-cell secretory capacity provides the best estimate of functional β-cell mass and is measured from glucose-potentiation of insulin or C-peptide release in response to a non-glucose secretagogue, such as arginine ( 22 ). In advanced type 2 diabetes (T2D), β-cell secretory capacity is diminished without a change in β-cell sensitivity to glucose ( 23 , 24 ), while early in T2D impaired β-cell sensitivity to glucose is present with relative preservation of the reserve capacity for insulin secretion that is evident with maximal glucose-potentiation ( 25 ). In contrast, we have demonstrated a decrease in β-cell secretory capacity in PI-CF subjects that progresses with worsening glucose tolerance status without any impairment in β-cell sensitivity to glucose ( 5 , 6 ).…”

Section: Discussionmentioning

confidence: 99%

Early-phase insulin secretion during mixed-meal tolerance testing predicts β-cell function and secretory capacity in cystic fibrosis

Sheikh,

Stefanovski,

Kilberg

et al. 2024

Front. Endocrinol.

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Insulin secretion within 30 minutes of nutrient ingestion is reduced in people with cystic fibrosis (PwCF) and pancreatic insufficiency and declines with worsening glucose tolerance. The glucose potentiated arginine (GPA) test is validated for quantifying β-cell secretory capacity as an estimate of functional β-cell mass but requires technical expertise and is burdensome. This study sought to compare insulin secretion during mixed-meal tolerance testing (MMTT) to GPA-derived parameters in PwCF.MethodsSecondary data analysis of CF-focused prospective studies was performed in PwCF categorized as 1) pancreatic insufficient [PI-CF] or 2) pancreatic sufficient [PS-CF] and in 3) non-CF controls. MMTT: insulin secretory rates (ISR) were derived by parametric deconvolution using 2-compartment model of C-peptide kinetics, and incremental area under the curve (AUC) was calculated for 30, 60 and 180-minutes. GPA: acute insulin (AIR) and C-peptide responses (ACR) were calculated as average post-arginine insulin or C-peptide response minus pre-arginine insulin or C-peptide under fasting (AIRarg and ACRarg), ~230 mg/dL (AIRpot and ACRpot), and ~340 mg/dL (AIRmax and ACRmax) hyperglycemic clamp conditions. Relationships of MMTT to GPA parameters were derived using Pearson’s correlation coefficient. Predicted values were generated for MMTT ISR and compared to GPA parameters using Bland Altman analysis to assess degree of concordance.Results85 PwCF (45 female; 75 PI-CF and 10 PS-CF) median (range) age 23 (6-56) years with BMI 23 (13-34) kg/m2, HbA1c 5.5 (3.8-10.2)%, and FEV1%-predicted 88 (26-125) and 4 non-CF controls of similar age and BMI were included. ISR AUC30min positively correlated with AIRarg (r=0.55), AIRpot (r=0.62), and AIRmax (r=0.46) and with ACRarg (r=0.59), ACRpot (r=0.60), and ACRmax (r=0.51) (all P<0.001). ISR AUC30min strongly predicted AIRarg (concordance=0.86), AIRpot (concordance=0.89), and AIRmax (concordance=0.76) at lower mean GPA values, but underestimated AIRarg, AIRpot, and AIRmax at higher GPA-defined β-cell secretory capacity. Between test agreement was unaltered by adjustment for study group, OGTT glucose category, and BMI.ConclusionEarly-phase insulin secretion during MMTT can accurately predict GPA-derived measures of β-cell function and secretory capacity when functional β-cell mass is reduced. These data can inform future multicenter studies requiring reliable, standardized, and technically feasible testing mechanisms to quantify β-cell function and secretory capacity.

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“…Our observation of an association of PIR with glucose metabolism that is independent of the metabolic syndrome is supported by a recent study showing increased proinsulin secretory ratios in non-obese participants with T2D compared with obese participants with T2D in response to a glucose-potentiated arginine test. 28 In turn, high HOMA-IR, indicating insulin resistance (eg, in overweight or obesity), may initially be related to a low PIR in pre-diabetes or NGT, resulting from a compensatory hypersecretion of insulin, whereas proinsulin levels initially remain constant, leading to a decreased or normal PIR. 17 29 30 At a later stage, when β-cell failure and T2D become apparent, proinsulin levels will increase disproportionately, resulting in an elevated PIR.…”

Section: Discussionmentioning

confidence: 99%

Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

Then

Gar

Thorand

et al. 2020

BMJ Open Diab Res Care

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IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006–2008)/FF4 study (2013–2014).Research design and methodsThe analyses included 1514 participants of the KORA F4 study at baseline and 1132 participants of the KORA FF4 study after a median follow-up time of 6.6 years. All-cause and cardiovascular mortality as well as cardiovascular events were analyzed after a median time of 9.1 and 8.6 years, respectively. The association of PIR with T2D, renal and cardiovascular characteristics and mortality were assessed using logistic regression models. Linear regression analyses were used to assess the association of PIR with components of the metabolic syndrome.ResultsAfter adjustment for sex, age, body mass index (BMI), and physical activity, PIR was associated with prevalent (OR: 2.24; 95% CI 1.81 to 2.77; p<0.001) and incident T2D (OR: 1.66; 95% CI 1.26 to 2.17; p<0.001). PIR was associated with fasting glucose (β per SD: 0.11±0.02; p<0.001) and HbA1c (β: 0.21±0.02; p<0.001). However, PIR was not positively associated with other components of the metabolic syndrome and was even inversely associated with waist circumference (β: −0.22±0.03; p<0.001), BMI (β: −0.11±0.03; p<0.001) and homeostatic model assessment of insulin resistance (β: −0.22±0.02; p<0.001). PIR was not significantly associated with the intima-media thickness (IMT), decline of kidney function, incident albuminuria, myocardial infarction, stroke, cardiovascular or all-cause mortality.ConclusionsIn the KORA F4/FF4 cohort, PIR was positively associated with prevalent and incident T2D, but inversely associated with waist circumference, BMI and insulin resistance, suggesting that PIR might serve as a biomarker for T2D risk independently of the metabolic syndrome, but not for microvascular or macrovascular complications.

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

Cited by 6 publications

References 24 publications

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

Early-phase insulin secretion during mixed-meal tolerance testing predicts β-cell function and secretory capacity in cystic fibrosis

Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

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