scholarly journals Plasma FGF-21 and Sclerostin Levels, Glycemia, Adiposity and Insulin Sensitivity in Normoglycemic Black and White Adults

2021 ◽  
Author(s):  
Nkiru Umekwe ◽  
Ibiye Owei ◽  
Frankie Stentz ◽  
Sam Dagogo-Jack
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Fibroblast Growth ◽  
Black And White ◽  
Fasting Plasma ◽  
White Adults

Abstract Increased circulating fibroblast growth factor (FGF)-21 and sclerostin levels have been reported in patients with type 2 diabetes (T2D). We assessed the association of FGF-21 and sclerostin with adiposity, glycemia and glucoregulatory measures in healthy subjects. We studied 20 normoglycemic Black and White offspring of parents with T2D. Assessments included OGTT, insulin sensitivity (Si-clamp), insulin secretion (HOMA-B), and body fat (DXA). Fasting plasma FGF-21 and sclerostin levels were measured with ELISAs. The participants' mean (+SD) age was 50.4 ± 5.97 yr; BMI 32.5 ± 5.86 kg/m2; fasting plasma glucose (FPG) 96.1 ± 5.21 mg/dl, and 2-hr post-load glucose (2hPG) 116 ± 5.45 mg/dl. FGF-21 levels were similar in Blacks vs. Whites (0.36 ± 0.15 ng/ml vs. 0.39 ± 0.25 ng/ml), men vs. women (0.45 ± 0.14 vs. 0.44 ± 0.07ng/ml), correlated positively with body mass index (BMI) (r=0.23, P=0.05) and waist circumference (r=0.27, P=0.04), and inversely with FPG (r= -0.26, P=0.05). Sclerostin levels also were similar in Blacks (33.5 ± 17.1 pmol/l) vs. Whites (34.2 ± 6.41 pmol/l), men vs. women (35.3 ± 9.01 pmol/l vs. 32.3 ± 15.8 pmol/l), and correlated inversely with FPG (r= - 0.11-0.44) but not adiposity measures. The correlation coefficient between Si-clamp values and FGF-21 levels was -0.31 (P=0.09) compared with 0.04 (P=0.89) for sclerostin levels. FGF-21 and sclerostin levels were not correlated with each other or HOMA-B. Among healthy Black and White subjects, plasma FGF-21 and sclerostin showed differential associations with adiposity but concordant association with FPG levels.

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.

scholarly journals Clinical Significance of the Maximum Body Mass Index Before Onset of Type 2 Diabetes for Predicting Beta-Cell Function

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Harutoshi Ozawa ◽  
Kenji Fukui ◽  
Sho Komukai ◽  
Yoshiya Hosokawa ◽  
Yukari Fujita ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Clinical Significance ◽  
Beta Cell Function ◽  
Cell Function ◽  
Duration Of Diabetes ◽  
Maximum Body

Abstract Objective This study aimed to clarify the clinical significance of the maximum body mass index (BMI) before the onset of type 2 diabetes (MBBO) for predicting pancreatic beta-cell function. Methods This was a cross-sectional observational study. Of 1304 consecutively admitted patients with type 2 diabetes, we enrolled 410 patients satisfying the criteria in this study. The correlations between the C-peptide index (CPI), which is one of the parameters that reflects beta-cell function, and various clinical parameters, including MBBO and duration of diabetes, were analyzed in multiple linear regression analyses. Results The analyses revealed that MBBO was correlated with CPI independently after adjustment for age, sex, HbA1c, and duration of diabetes. When we divided the subjects into three subgroups by MBBO (MBBO &lt; 25 kg/m2; 25 kg/m2 ≤ MBBO &lt; 30 kg/m2; MBBO ≥ 30 kg/m2), CPI was negatively correlated with duration of diabetes in each subgroup, while the rates of CPI based on the duration of diabetes were not different among the three MBBO subgroups. In contrast, the declining rates of CPI were higher in the BMI ≥ 25 kg/m2 group on admission than in the BMI &lt; 25 kg/m2 group on admission. Conclusions MBBO may be an independent factor correlating with beta-cell function and may predict insulin secretion capacity at diagnosis, but it does not seem to affect the rate of decline in insulin secretion capacity after diagnosis. It is important to preserve beta-cell function by decreasing a patient’s BMI during treatment after diagnosis regardless of MBBO.

scholarly journals Associations of Glucose Control with Insulin Sensitivity and Pancreatic β-Cell Responsiveness in Newly Presenting Type 2 Diabetes

2002 ◽  
Vol 87 (1) ◽  
pp. 198-203 ◽  
Author(s):  
Ahmed I. Albarrak ◽  
Stephen D. Luzio ◽  
Ludovic J. Chassin ◽  
Rebecca A. Playle ◽  
David R. Owens ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Glucose Control ◽  
Interindividual Variability ◽  
Postprandial Glucose ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Fasting Plasma

We examined the ability of indices of insulin sensitivity and pancreatic β-cell responsiveness to explain interindividual variability of clinical measures of glucose control in newly presenting type 2 diabetes. Subjects with newly presenting type 2 diabetes (n = 65; 53 males and 12 females; age, 54 ± 1 yr; body mass index, 30.5 ± 0.7 kg/m2; mean ± se) underwent an insulin-modified iv glucose tolerance test to determine minimal model-derived insulin sensitivity (SI), glucose effectiveness, first-phase insulin secretion, and disposition index. Subjects also underwent a standard meal tolerance test (MTT) to measure fasting/basal (M0) and postprandial (MI) pancreatic β-cell responsiveness. Stepwise linear regression used these indices to explain interindividual variability of fasting and postprandial plasma glucose and insulin concentrations and glycated hemoglobin (HbA1C). All measures of pancreatic β-cell responsiveness (M0, MI, and first-phase insulin secretion) were negatively correlated with fasting plasma glucose (P &lt; 0.01) and positively correlated with fasting plasma insulin (FPI) and insulin responses to MTT (P &lt; 0.05). SI demonstrated negative correlation with FPI (P &lt; 0.001) but failed to correlate with any glucose variable. MI followed by disposition index (composite index of insulin sensitivity and pancreatic β-cell responsiveness) were most informative in explaining interindividual variability. It was possible to explain 70–80% interindividual variability of fasting plasma glucose, FPI, HbA1C, and insulin responses to MTT, and only 25–40% interindividual variability of postprandial glucose. In conclusion, postprandial insulin deficiency is the most powerful explanatory factor of deteriorating glucose control in newly presenting type 2 diabetes. Indices of insulin sensitivity and pancreatic β-cell responsiveness explain fasting glucose and HbA1C well but fail to explain postprandial glucose.

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.

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