Impact of glucagon response on early‐postprandial glucose excursions irrespective of residual β‐cell function in type 1 diabetes: A cross‐sectional study using a mixed‐meal tolerance test

Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 μg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.

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Association of Insulin Resistance and β-cell Function With Bone Turnover Biomarkers in Dysglycemia Patients

Frontiers in Endocrinology ◽

10.3389/fendo.2021.554604 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hui Guo ◽

Chiyu Wang ◽

Boren Jiang ◽

Shaohong Ge ◽

Jian Cai ◽

...

Keyword(s):

Insulin Resistance ◽

Bone Turnover ◽

Type I Collagen ◽

Cell Function ◽

Cross Sectional Study ◽

Type I ◽

Model Assessment ◽

Β Cell ◽

Cross Sectional ◽

Β Cell Function

BackgroundThe interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, β-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism.MethodsA total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.chictr.org.cn, ChiCTR1800017573) in Shanghai, China. Homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell dysfunction (HOMA-%β) were applied to elucidate the nexus between β-C-terminal telopeptide (β-CTX), intact N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). β-CTX, OC and P1NP were detected by chemiluminescence.ResultsHOMA-IR was negatively associated with β-CTX, P1NP and OC (regression coefficient (β) -0.044 (-0.053, -0.035), Q4vsQ1; β -7.340 (-9.130, -5.550), Q4vsQ1 and β -2.885 (-3.357, -2.412), Q4vsQ1, respectively, all P for trend <0.001). HOMA-%β was positively associated with β-CTX, P1NP and OC (β 0.022 (0.014, 0.031), Q4vsQ1; β 6.951 (5.300, 8.602), Q4vsQ1 and β 1.361 (0.921, 1.800), Q4vsQ1, respectively, all P for trend <0.001).ConclusionsOur results support that lower bone turnover biomarker (β-CTX, P1NP and OC) levels were associated with a combination of higher prevalence of insulin resistance and worse β-cell function among dysglycemia patients. It is feasible to detect bone turnover in diabetes or hyperglycemia patients to predict the risk of osteoporosis and fracture, relieve patients’ pain and reduce the expenses of long-term cure.

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OGTT Glucose Response Curves, Insulin Sensitivity, and β-Cell Function in RISE: Comparison Between Youth and Adults at Randomization and in Response to Interventions to Preserve β-Cell Function

10.2337/figshare.13373708.v1 ◽

2021 ◽

Author(s):

Silva Arslanian ◽

Laure El ghormli ◽

Joon Young Kim ◽

Ashley H. Tjaden ◽

Elena Barengolts ◽

...

Keyword(s):

Insulin Sensitivity ◽

B Cell ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Β Cell ◽

Response Curves ◽

Glucose Response ◽

Cross Sectional ◽

Β Cell Function

Objective: We examined the glucose-response-curves [Biphasic (BPh), Monophasic (MPh), Incessant-Increase (IIn)], during an oral glucose tolerance test (OGTT), and their relationship to insulin sensitivity (IS) and b-cell function (bCF) in youth vs. adults with IGT or recently diagnosed type 2 diabetes. Research Design and Methods: This was both a cross-sectional and longitudinal evaluation of participants in the RISE study randomized to metformin alone for 12 months or glargine for 3 months followed by metformin for 9 months. At baseline/randomization, OGTTs (85 youth, 353 adults) were categorized as BPh, MPh, or IIn. The relationship of the glucose-response-curves to hyperglycemic-clamp-measured IS and bCF at baseline, and the change in glucose-response-curves 12 months after randomization were assessed. Results: At randomization, the prevalence of the BPh-curve was significantly higher in youth than adults (18.8% vs. 8.2%), with no differences in MPh or IIn. IS did not differ across glucose-response-curves in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p<0.05). bCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05). Yet, compared with adults, youth had higher bCF in BPh and MPh (p<0.005), but not IIn curves. At month 12, the change in glucose-response-curves did not differ between youth and adults, and there was no treatment effect. Conclusions: Despite a 2-fold higher prevalence of the more-favorable BPh curve in youth at randomization, RISE interventions did not result in beneficial changes in glucose-response-curves in youth compared with adults. Moreover, the typical b-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of b-cell dysfunction in youth with this least- favorable glucose-response-curve.

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Residual β-Cell Function and the Insulin-Like Growth Factor System in Danish Children and Adolescents With Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3521 ◽

2015 ◽

Vol 100 (3) ◽

pp. 1053-1061 ◽

Cited By ~ 14

Author(s):

Jesper S. Sorensen ◽

Niels H. Birkebaek ◽

Mette Bjerre ◽

Flemming Pociot ◽

Kurt Kristensen ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cell Function ◽

Β Cell ◽

Cross Sectional ◽

Prepubertal Children ◽

C Peptide ◽

Pubertal Status ◽

Igf System ◽

Β Cell Function

Context: C-peptide-positive adults with type 1 diabetes (T1D) have higher circulating total and free IGF-1 and lower IGF binding protein 1 (IGFBP-1) than C-peptide-negative patients. Whether this is also the case in children remains unknown. Objective: The objective of the study was to examine the IGF system in children/adolescents with and without residual β-cell function (RBF). Design and Patients: This was a cross-sectional study containing 136 prepubertal (hereof 15 RBF positive) and 206 pubertal (hereof 42 RBF positive) children/adolescents with T1D for 3–6 years as well as 40 prepubertal and 30 pubertal healthy controls. RBF was evaluated by meal-stimulated C-peptide. Main Outcome Measures: Fasting serum levels of bioactive IGF (ie, the ability of serum to activate the IGF-1 receptor in vitro), total IGF-1, total IGF-2, and IGFBP-1 and -3. Results: Irrespective of pubertal status, patients with T1D showed lower bioactive IGF and total IGF-1, but higher IGFBP-1 as compared with controls (P < .05). When stratified according to RBF status, a positive RBF was associated with normalization of all IGF-related peptides but IGFBP-1 in prepubertal children (P < .05), whereas none of the IGF components were normalized in prepubertal, RBF-negative children. In pubertal children, total IGF-1 and bioactive IGF remained subnormal and IGFBP-1 supranormal, irrespective of RBF status (P < .05). Conclusion: Independent of pubertal status, T1D was associated with an abnormal IGF system. However, a positive RBF status appeared important but only in prepubertal children, in whom all IGF components but IGFBP-1 were normalized. We speculate that the pubertal GH surge induces insulin resistance, which overrides the stimulatory effect that an RBF may exert on the liver-derived IGF system.

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