Similar weight-adjusted insulin secretion and insulin sensitivity in short-duration late autoimmune diabetes of adulthood (LADA) and Type 2 diabetes: Action LADA 8

2014 ◽  
Vol 31 (8) ◽  
pp. 941-945 ◽  
Author(s):  
C. B. Juhl ◽  
U. Bradley ◽  
J. J. Holst ◽  
R. D. Leslie ◽  
K. B. Yderstraede ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Short Duration ◽  
Autoimmune Diabetes ◽  
Similar Weight

Association of plasma acylcarnitines with insulin sensitivity, insulin secretion, and prediabetes in a biracial cohort

2021 ◽  
pp. 153537022110094
Author(s):  
Ibiye Owei ◽  
Nkiru Umekwe ◽  
Frankie Stentz ◽  
Jim Wan ◽  
Sam Dagogo-Jack
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Intravenous Glucose Tolerance Test ◽  
Cross Sectional ◽  
Parental History ◽  
Intravenous Glucose

The ability to predict prediabetes, which affects ∼90 million adults in the US and ∼400 million adults worldwide, would be valuable to public health. Acylcarnitines, fatty acid metabolites, have been associated with type 2 diabetes risk in cross-sectional studies of mostly Caucasian subjects, but prospective studies on their link to prediabetes in diverse populations are lacking. Here, we determined the association of plasma acylcarnitines with incident prediabetes in African Americans and European Americans enrolled in a prospective study. We analyzed 45 acylcarnitines in baseline plasma samples from 70 adults (35 African-American, 35 European-American) with incident prediabetes (progressors) and 70 matched controls (non-progressors) during 5.5-year (mean 2.6 years) follow-up in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Incident prediabetes (impaired fasting glucose/impaired glucose tolerance) was confirmed with OGTT. We measured acylcarnitines using tandem mass spectrometry, insulin sensitivity by hyperinsulinemic euglycemic clamp, and insulin secretion using intravenous glucose tolerance test. The results showed that progressors and non-progressors during POP-ABC study follow-up were concordant for 36 acylcarnitines and discordant for nine others. In logistic regression models, beta-hydroxy butyryl carnitine (C4-OH), 3-hydroxy-isovaleryl carnitine/malonyl carnitine (C5-OH/C3-DC), and octenoyl carnitine (C8:1) were the only significant predictors of incident prediabetes. The combined cut-off plasma levels of <0.03 micromol/L for C4-OH, <0.03 micromol/L for C5-OH/C3-DC, and >0.25 micromol/L for C8:1 acylcarnitines predicted incident prediabetes with 81.9% sensitivity and 65.2% specificity. Thus, circulating levels of one medium-chain and two short-chain acylcarnitines may be sensitive biomarkers for the risk of incident prediabetes among initially normoglycemic individuals with parental history of type 2 diabetes.

scholarly journals The Effect of Standard versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients with Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass. The Long-Limb study

2020 ◽  
Author(s):  
Alexander Dimitri Miras ◽  
Anna Kamocka ◽  
Belén Pérez-Pevida ◽  
Sanjay Purkayastha ◽  
Krishna Moorthy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Mechanistic Study ◽  
Intestinal Bypass ◽  
Distal Small Intestine ◽  
Time To Peak ◽  
Biliopancreatic Limb

Objective <p>Roux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial levels of Glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial peak in GLP-1, translating into higher insulin secretion and thus additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.</p> <p>Research Design and Methods</p> <p>Fifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery.</p> <p>Results</p> <p>Both groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. </p> <p>Conclusion</p> The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Cerivastatin improves insulin sensitivity and insulin secretion in early-state obese type 2 diabetes

2003 ◽  
Vol 15 (6) ◽  
pp. 282-284
Author(s):  
J.A. Paniagua ◽  
J. López-Miranda ◽  
A. Escribano ◽  
F.J. Berral ◽  
C. Marín ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Early State

scholarly journals Phenotypic and Molecular Evaluation of a Chromosome 1q Region with Linkage and Association to Type 2 Diabetes in Humans

2009 ◽  
Vol 94 (4) ◽  
pp. 1401-1408 ◽  
Author(s):  
Hua Wang ◽  
Nicholas P. Hays ◽  
Swapan K. Das ◽  
Rebekah L. Craig ◽  
Winston S. Chu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Linkage Disequilibrium Block ◽  
Glucose Production ◽  
Risk Haplotype ◽  
Expression Of Genes ◽  
Hepatic Glucose

Abstract Objective: Linkage to type 2 diabetes (T2D) is well replicated on chromosome 1q21-q23. Within this region, T2D was associated with common single nucleotide polymorphisms that marked an extended linkage disequilibrium block, including the liver pyruvate kinase gene (PKLR), in several European-derived populations. In this study we sought to determine the molecular basis for the association and the phenotypic consequences of the risk haplotype. Research Design and Methods: Genes surrounding PKLR were resequenced in European-American and African-American cases and controls, and association with T2D was tested. Copy number variants (CNVs) were tested for four regions with real-time PCR. Expression of genes in the region was tested in adipose and muscle from nondiabetic subjects with each genotype. Insulin secretion, insulin sensitivity, and hepatic glucose production were tested in nondiabetic individuals with each haplotype combination. Results: No coding variant in the region was associated with T2D. CNVs were rare and not associated with T2D. PKLR was not expressed in available tissues, but expression of genes HCN3, CLK2, SCAMP3, and FDPS was not associated with haplotype combinations in adipose or muscle. Haplotype combinations were not associated with insulin secretion or peripheral insulin sensitivity, but homozygous carriers of the risk haplotype had increased hepatic glucose production during hyperinsulinemia. Conclusions: Noncoding variants in the PKLR region likely alter gene expression of one or more genes. Our extensive physiological and molecular studies suggest increased hepatic glucose production and reduced hepatic insulin sensitivity, thus pointing to PKLR itself as the most likely candidate gene in this population.

Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
Author(s):  
Christoffer Martinussen ◽  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Siv H. Jacobsen ◽  
Nils B. Jørgensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Glucose Effectiveness ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

scholarly journals Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index

2021 ◽  
Author(s):  
Elsa Vazquez Arreola ◽  
Robert L. Hanson ◽  
Clifton Bogardus ◽  
William C. Knowler
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Allostatic Load ◽  
Regression Line ◽  
Epidemiologic Study ◽  
Disposition Index ◽  
Lower Sensitivity ◽  
The Relationship

We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all subjects did not have diabetes, 1566 participants underwent oral tests and 420 had intravenous measures of glucose regulation with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship of secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relationship differed according to glucose tolerance and BMI categories. The distance away from the line is similar to the disposition index (DI) defined as the product of estimated secretion and sensitivity, but the regression line may differ from a line with constant DI (i.e., it is not necessarily hyperbolic). Subjects with the same DI but different levels of insulin secretion and sensitivity had different incidence rates of diabetes; lower sensitivity with higher secretory demand was associated with greater diabetes risk. Insulin secretion and insulin sensitivity, analyzed together, predict diabetes better than DI alone. Physiologically, this may reflect long-term risk associated with increased allostatic load resulting from the stimulation of insulin hypersecretion by increased glycemia.

scholarly journals Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index

2021 ◽  
Author(s):  
Elsa Vazquez Arreola ◽  
Robert L. Hanson ◽  
Clifton Bogardus ◽  
William C. Knowler
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Allostatic Load ◽  
Regression Line ◽  
Epidemiologic Study ◽  
Disposition Index ◽  
Lower Sensitivity ◽  
The Relationship

We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all subjects did not have diabetes, 1566 participants underwent oral tests and 420 had intravenous measures of glucose regulation with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship of secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relationship differed according to glucose tolerance and BMI categories. The distance away from the line is similar to the disposition index (DI) defined as the product of estimated secretion and sensitivity, but the regression line may differ from a line with constant DI (i.e., it is not necessarily hyperbolic). Subjects with the same DI but different levels of insulin secretion and sensitivity had different incidence rates of diabetes; lower sensitivity with higher secretory demand was associated with greater diabetes risk. Insulin secretion and insulin sensitivity, analyzed together, predict diabetes better than DI alone. Physiologically, this may reflect long-term risk associated with increased allostatic load resulting from the stimulation of insulin hypersecretion by increased glycemia.

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