scholarly journals Discordant association of the CREBRF rs373863828 minor allele with increased body mass index and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa New Zealand

2017 ◽  
Author(s):  
Mohanraj Krishnan ◽  
Tanya J Major ◽  
Ruth K Topless ◽  
Ofa Dewes ◽  
Lennex Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
New Zealand ◽  
Waist Circumference ◽  
Body Mass ◽  
American Samoa ◽  
Minor Allele ◽  
Association Analyses ◽  
Aotearoa New Zealand

AbstractAim/HypothesesThe minor allele of CREBRF rs373863828 associates with increased body mass index (BMI) and reduced risk of type 2 diabetes (T2D) in the Samoan population of Samoa and American Samoa. Our aim was to test rs373863828 for association with BMI and odds of T2D, gout and chronic kidney disease (CKD) in Māori and Pacific (Polynesian) people living in Aotearoa New Zealand in 2,286 adults.MethodsAssociation analyses were performed by linear and logistic regression with BMI, log-transformed BMI, waist circumference, T2D, gout and CKD. Analyses were adjusted for age, sex, the first four genome-wide principal components, and (when appropriate) BMI, waist circumference and T2D.ResultsFor the minor allele of rs373863828 the effect size for log-transformed BMI was 0.038 (95% CI [0.022-0.055], P=4.8x10−6) and for T2D was OR=0.59 (95% CI [0.47-0.73], P=1.9x10−6). There was no evidence for association of genotype with variance in BMI (P=0.13). Nor was there evidence for association with serum urate (β=0.012 mmol/L, Pc=0.10), gout (OR=1.00, P=0.98) or CKD (OR=0.91, P=0.59).Conclusions/interpretationOur results replicated, with very similar effect sizes, association of the minor allele of rs373863828 with higher BMI but lower odds of T2D among New Zealand Polynesian adults, as in Samoan adults living in Samoa and American Samoa.

scholarly journals CREBRF missense variant rs373863828 has both direct and indirect effects on type 2 diabetes and fasting glucose in Polynesians living in Samoa and Aotearoa New Zealand

2021 ◽  
Author(s):  
Emily M. Russell ◽  
Jenna C. Carlson ◽  
Mohanraj Krishnan ◽  
Nicola L. Hawley ◽  
Guangyun Sun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
New Zealand ◽  
Path Analysis ◽  
Fasting Glucose ◽  
Missense Variant ◽  
American Samoa ◽  
Minor Allele ◽  
Positive Effects ◽  
Aotearoa New Zealand

AbstractObjectiveThe minor allele of rs373863828 in CREBRF is associated with higher BMI, lower fasting glucose, and lower odds of type 2 diabetes. We examined the associations between BMI and rs373863828 on type 2 diabetes and fasting glucose with a large sample of adult Polynesians from Samoa, American Samoa and Aotearoa New Zealand and estimated direct and indirect (via BMI) effects of rs373863828 on type 2 diabetes and fasting glucose.Research Design and MethodsWe regressed type 2 diabetes and fasting glucose on BMI and rs373863828 stratified by obesity, regressed type 2 diabetes and fasting glucose on BMI stratified by rs373863828 genotype, and assessed the effects of rs373863828 on type 2 diabetes and fasting glucose with path analysis.ResultsAssociation of BMI with fasting glucose was greater in those without obesity than in those with obesity. We did not observe evidence of differences by genotype. In the path analysis, the minor allele has direct negative and indirect positive effects on type 2 diabetes risk and fasting glucose, with the indirect effect mediated through a direct positive effect on BMI.ConclusionsThere may be a stronger effect of BMI on fasting glucose in Polynesians without obesity than in those with obesity. Carrying the rs373863828 minor allele does not decouple higher BMI from odds of type 2 diabetes. Given the current cost of genotyping compared to the accessibility of measuring BMI, including rs373863828 as a clinical predictor of type 2 diabetes may not be indicated.

scholarly journals The effects of metformin plus sulfonylurea therapy on clinical features of the metabolic syndrome

2010 ◽  
Vol 63 (9-10) ◽  
pp. 611-615 ◽  
Author(s):  
Branka Koprivica ◽  
Teodora Beljic-Zivkovic ◽  
Tatjana Ille
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Glycemic Control ◽  
Body Mass ◽  
Combined Therapy

Introduction. Insulin resistance is a well-known leading factor in the development of metabolic syndrome. The aim of this study was to evaluate metabolic effects of metformin added to sulfonylurea in unsuccessfully treated type 2 diabetic patients with metabolic syndrome. Material and methods. A group of thirty subjects, with type 2 diabetes, secondary sulfonylurea failure and metabolic syndrome were administered the combined therapy of sulfonylurea plus metformin for six months. Metformin 2000 mg/d was added to previously used sulfonylurea agent in maximum daily dose. Antihypertensive and hypolipemic therapy was not changed. The following parameters were assessed at the beginning and after six months of therapy: glycemic control, body mass index, waist circumference, blood pressure, triglycerides, total cholesterol and its fractions, homeostatic models for evaluation of insulin resistance and secretion (HOMA R, HOMA B) and C- peptide. Results. Glycemic control was significantly improved after six months of the combined therapy: (fasting 7.89 vs. 10.61 mmol/l. p<0.01; postprandial 11.12 vs. 12.61 mmol/l. p<0.01, p<0.01; glycosylated hemoglobin 6.81 vs. 8.83%. p<0.01). the body mass index and waist circumference were significantly lower (26.7 vs. 27.8 kg/m2, p<0.01 and 99.7 vs. 101.4 cm for men, p<0.01; 87.2 vs. 88.5 for women, p<0.01). Fasting plasma triglycerides decreased from 3.37 to 2.45 mmol/l (p<0.001) and HOMA R from 7.04 to 5.23 (p<0.001). No treatment effects were observed on blood pressure, cholesterol, and residual insulin secretion. Conclusion. Administration of metformin in type 2 diabetes with metabolic syndrome decreased cardiovascular risk factors by reducing glycemia, triglycerides, BMI, central obesity and insulin resistance.

scholarly journals Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls

2015 ◽  
Vol 119 (9) ◽  
pp. 953-960 ◽  
Author(s):  
C. Ekman ◽  
T. Elgzyri ◽  
K. Ström ◽  
P. Almgren ◽  
H. Parikh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Body Mass ◽  
Exercise Intervention ◽  
Peak Oxygen Consumption ◽  
Cellular Respiration ◽  
Muscle Adaptation ◽  
Response To Exercise

Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility compared with subjects without heredity for diabetes (FH−). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared with FH−. Sixteen FH+ and 19 FH− insulin-sensitive men similar in age, peak oxygen consumption (V̇o2 peak), and body mass index completed an exercise intervention with heart rate monitored during exercise for 7 mo. Before and after the exercise intervention, the participants underwent a physical examination and tests for glucose tolerance and exercise capacity, and muscle biopsies were taken for expression analysis. The participants attended, on average, 39 training sessions during the intervention and spent 18.8 MJ on exercise. V̇o2 peak/kg increased by 14%, and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH+ group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH− groups separately. Exercise volume had a significant effect on V̇o2 peak, weight, and waist circumference in the FH− group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation, and cellular respiration increased more in the FH− compared with the FH+ group. This suggests that healthy, insulin-sensitive FH+ and FH− participants with similar age, V̇o2 peak, and body mass index may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals.

scholarly journals The effect of combination therapy of insulin glargine, metformin, and sitagliptin on insulin secretion, insulin resistance, and metabolic parameters in obese subjects with type 2 diabetes

2016 ◽  
Vol 144 (9-10) ◽  
pp. 497-502
Author(s):  
Teodora Beljic-Zivkovic ◽  
Milica Marjanovic-Petkovic ◽  
Miljanka Vuksanovic ◽  
Ivan Soldatovic ◽  
Dobrila Kanlic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Insulin Glargine ◽  
Body Mass ◽  
Fasting Glucose ◽  
C Peptide ◽  
Obese Subjects

Introduction. A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity. Objective. Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes. Methods. A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated. Results. Participants were 58.65 ?} 7.62 years of age with a body mass index of 35.06 ?} 5.15 kg/m2, waist circumference of 115.04 ?} 15.5 cm, and the duration of diabetes of 4.11 ?} 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged. Conclusion. Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.

scholarly journals Association between Sex Hormone and Blood Uric Acid in Male Patients with Type 2 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wen Cao ◽  
Ren-Dong Zheng ◽  
Shu-Hang Xu ◽  
Yao-Fu Fan ◽  
Hong-Ping Sun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Uric Acid ◽  
Waist Circumference ◽  
Serum Uric Acid ◽  
Body Mass ◽  
Sex Hormone ◽  
Gonadal Dysfunction ◽  
Male Patients

The association between serum uric acid (SUA) level and sexual dysfunction in patients with diabetes is not well characterized. Type 2 diabetes mellitus (T2DM) causes metabolic disorders, including abnormal serum uric acid (SUA) levels. In this study, we enrolled 205 male patients with T2DM and investigated the relationship between sex hormone levels and SUA. Patients were divided into four groups based on SUA quartiles. On the other hand, based on the total testosterone (TT) level, patients were divided into three groups; SUA and other laboratory indices were determined. Increase in SUA level was significantly associated with decreased levels of TT, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, and increased levels of dehydroepiandrosterone, age, body mass index (BMI), waist circumference, glycated hemoglobin, serum creatinine, and HOMA-IR levels. SUA, waist circumference, BMI, and HOMA-IR showed a negative correlation with TT level, while age showed a positive correlation with TT level. SUA and body mass index were found to be risk factors for gonadal dysfunction. Therefore, we conclude that hypogonadism of male patients with T2DM is related to SUA level.

Statistical issues in studying the relative importance of body mass index, waist circumference, waist hip ratio and waist stature ratio to predict type 2 diabetes

2011 ◽  
Vol 38 (9) ◽  
pp. 2063-2070 ◽  
Author(s):  
Bhamidipati Narasimha Murthy ◽  
Ngianga-Bakwin Kandala ◽  
Radhakrishnan Ezhil ◽  
Prabhdeep Kaur ◽  
Ramachandra Sudha
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Body Mass ◽  
Relative Importance ◽  
Waist Hip Ratio ◽  
Statistical Issues
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