scholarly journals Analysis of Osteocalcin as a Candidate Gene for Type 2 Diabetes (T2D) and Intermediate Traits in Caucasians and African Americans

2010 ◽  
Vol 28 (5) ◽  
pp. 281-286 ◽  
Author(s):  
Swapan K. Das ◽  
Neeraj K. Sharma ◽  
Steven C. Elbein
Keyword(s):  
Type 2 Diabetes ◽  
African American ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Nucleotide Polymorphisms ◽  
Case Control Studies

Recent studies in mice and human identified osteocalcin (OCN) as a bone-derived hormone that modulates insulin secretion and insulin sensitivity. OCN is synthesized by the bone gamma-carboxyglutamate protein (BGLAP) gene located in the well replicated region of type 2 diabetes (T2D) linkage on chromosome 1q22. We resequencedBGLAPgene in 192 individuals with T2D and performed case-control studies in 766 Caucasian (461 T2D and 305 controls) and 563 African American individuals (371 T2D and 192 controls). Metabolic effects ofBGLAPvariants were examined in 127 nondiabetic members of Caucasian T2D families and in 498 unrelated nondiabetic African American and Caucasian individuals.BGLAPexpression was tested in transformed lymphocytes from 60 Caucasian individuals. We identified 17 single nucleotide polymorphisms (SNPs) in African Americans, but observed only the two known SNPs in Caucasians. No SNP was associated with T2D. Promoter SNP rs1800247 was not associated with metabolic traits including insulin sensitivity (SI) or fasting glucose in either population, but nonsynonymous SNP rs34702397 (R94Q) was nominally associated with SI(uncorrectedp= 0.05) and glucose-mediated glucose disposal (SG; uncorrectedp= 0.03) in African Americans. No SNP altered measures of insulin secretion or obesity, nor wasBGLAPexpression associated with rs1800247. Our study was sufficiently powered to excludeBGLAPvariants as a major risk factor (OR > 1.5) for T2D in Caucasians, but coding variants in exon 4 may alter glucose homeostasis and diabetes risk in African Americans.

scholarly journals Effect of meal timing and glycaemic index on glucose control and insulin secretion in healthy volunteers

2011 ◽  
Vol 108 (7) ◽  
pp. 1286-1291 ◽  
Author(s):  
Linda M. Morgan ◽  
Jiang-Wen Shi ◽  
Shelagh M. Hampton ◽  
Gary Frost
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Control ◽  
High Energy ◽  
Glycaemic Index ◽  
Metabolic Effects ◽  
Meal Timing ◽  
Daily Energy

Shiftworkers have a higher risk of CHD and type 2 diabetes. They consume a large proportion of their daily energy and carbohydrate intake in the late evening or night-time, a factor which could be linked to their increase in disease risk. We compared the metabolic effects of varying both dietary glycaemic index (GI) and the time at which most daily energy intake was consumed. We hypothesised that glucose control would be optimal with a low-GI diet, consumed predominantly early in the day. A total of six healthy lean volunteers consumed isoenergetic meals on four occasions, comprising either high- or low-GI foods, with 60 % energy consumed predominantly early (breakfast) or late (supper). Interstitial glucose was measured continuously for 20 h. Insulin, TAG and non-esterified fatty acids were measured for 2 h following every meal. Highest glucose values were observed when large 5021 kJ (1200 kcal) high-GI suppers were consumed. Glucose levels were also significantly higher in predominantly late high- v. low-GI meals (P < 0·01). Using an estimate of postprandial insulin sensitivity throughout the day, we demonstrate that this follows the same trend, with insulin sensitivity being significantly worse in high energy consumed in the evening meal pattern. Both meal timing and GI affected glucose tolerance and insulin secretion. Avoidance of large, high-GI meals in the evening may be particularly beneficial in improving postprandial glucose profiles and may play a role in reducing the risk of type 2 diabetes; however, longer-term studies are needed to confirm this.

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 Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects

2006 ◽  
Vol 7 (1) ◽  
Author(s):  
Steven C Elbein ◽  
Xiaoqin Wang ◽  
Mohammad A Karim ◽  
Winston S Chu ◽  
Kristi D Silver
Keyword(s):  
Type 2 Diabetes ◽  
African American ◽  
Insulin Secretion ◽  
Coding Variants

scholarly journals Molecular Screening and Association Analyses of the Interleukin 6 Receptor Gene Variants with Type 2 Diabetes, Diabetic Nephropathy, and Insulin Sensitivity

2005 ◽  
Vol 90 (2) ◽  
pp. 1123-1129 ◽  
Author(s):  
Hua Wang ◽  
Zhengxian Zhang ◽  
Winston Chu ◽  
Terri Hale ◽  
Judith J. Cooper ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Insulin Sensitivity ◽  
Single Nucleotide Polymorphisms ◽  
Untranslated Region ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Northern European ◽  
A Minor

IL-6 levels and polymorphisms have been implicated in type 2 diabetes mellitus (T2DM) and insulin resistance. The IL-6 receptor (IL-6R) comprises two subunits, IL-6R and gp130, of which IL-6R confers specificity to IL-6 action and is located in a region of replicated linkage to T2DM on chromosome 1q21. We screened this gene for variation in Northern European Caucasian and African-American ethnic groups. We identified 11 variants with a minor allele frequency over 5%, including two amino acid changes (D358A and V385I) and four variants in the 3′ untranslated region. No variant was associated with obesity or measures of insulin sensitivity, but two single nucleotide polymorphisms in the 3′ untranslated region showed a trend to an association with T2DM in all Caucasians, and three single nucleotide polymorphisms, including D358A, showed a trend (P &lt; 0.06) to an association with T2DM among the subset of Northern European Caucasians. Variant V385I was unique to African-Americans and was significantly associated with diabetes and diabetic nephropathy (P &lt; 0.05). Among individuals heterozygous for the four variants in the transcribed sequence, one allele was significantly overrepresented, thus suggesting the existence of a regulatory variant controlling mRNA stability or expression. IL-6R is not likely to explain the linkage to diabetes in this region, but our work supports a minor role of variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA levels and possibly levels of soluble IL-6R.

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
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