Associations of SRD5A1 gene variants and testosterone with dysglycemia: Henan Rural Cohort study.

BACKGROUND AND AIM: Multiple studies support a complex relationship between testosterone and type 2 diabetes mellitus (T2DM) and the transformation of testosterone is affected by several reductases. Thus, we aimed to explore the associations of steroid-5α-reductase type 1 (SRD5A1) gene polymorphism with impaired fasting glucose (IFG) and T2DM and the interactive effects of testosterone and genotypes on glycometabolism. METHODS AND RESULTS: A case-control study including 2365 participants was performed. Genomic DNA was extracted from the whole blood and genotyped for the SRD5A1 single nucleotide polymorphisms (SNP) rs1691053. Multivariable logistic regression and linear regression were performed to estimate the associations of SRD5A1 rs1691053 alleles and genotypes with glycometabolism. Generalized linear models were used to investigate the modulatory effects of serum testosterone on glycometabolism indexes in males. After multivariable adjustment, the odds ratio (OR) of homozygous CC genotypes in male carriers was 2.62 (95%CI: 1.11-6.18) for IFG. Furthermore, significant associations of SRD5A1 rs1691053 polymorphisms with adverse indices of glycometabolism were observed in males. Interestingly, the opposite associations in females were observed. The interactive associations of SNP and testosterone were found and mutations were more likely to lead unfavorable metabolic phenotypes. CONCLUSION: These results showed that SRD5A1 rs1691053 gene polymorphism was independently associated with glycometabolism. The interaction between a genetic polymorphism from SRD5A1 and testosterone involved glycometabolism was identified in males. Although this preliminary data should be replicated with other rigorous researches, it highlighted the importance of the SNP-testosterone interaction over the present of glycometabolism.

Racial differences in performance of HbA1c for the classification of diabetes and prediabetes among US adults of non-Hispanic black and white race.

AIM: To characterize differences between black and white people in optimal HbA1c thresholds for diagnoses of diabetes and prediabetes. METHODS: Data were included from the National Health and Nutrition Examination Survey, 2005-2014. Black and white adults (age 18-70 years) who underwent an oral glucose tolerance test and had available fasting plasma glucose, 2-h plasma glucose and HbA1c measurements were eligible for inclusion. Diabetes or prediabetes status was defined by fasting plasma glucose and 2-h plasma glucose using American Diabetes Association criteria. Classification of diabetes, prediabetes and dysglycaemia by HbA1c was evaluated for a range of HbA1c thresholds, with optimal thresholds defined as those values that maximized the sum of sensitivity and specificity (Youden's index). RESULTS: In 5324 black (32.3%) and white (67.7%) individuals, Youden's index (optimal) thresholds for HbA1c were ≥42 mmol/mol (6.0%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs non-diabetes, ≥ 44 mmol/mol (6.2%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs prediabetes (excluding normoglycaemia), ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating dysglycaemia vs normoglycaemia, and ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating prediabetes vs normoglycaemia (excluding diabetes), in black and white people, respectively. CONCLUSIONS: Consistently higher optimal HbA1c thresholds in black people than in white people suggest a need to individualize HbA1c relative to glucose levels if HbA1c is used to diagnose diabetes and prediabetes.

One-hour post-load plasma glucose predicts progression to prediabetes in a multi-ethnic cohort of obese youths.

AIMS: One-hour post-load hyperglycaemia has been proposed as an independent predictor of type 2 diabetes in adults. We examined whether 1-hour plasma glucose (1hPG) during an oral glucose tolerance test (OGTT) can predict changes in the glucose tolerance status of a multi-ethnic cohort of youths with normal glucose tolerance (NGT). MATERIALS AND METHODS: A total of 202 obese youths with NGT (33.7% Caucasian, 31.1% Hispanic, 32.2% African American) underwent a 3-hour OGTT at baseline and after a 2-year follow-up period. Whole-body insulin sensitivity, insulin secretion, ß-cell function and insulin clearance were estimated by modeling plasma glucose, insulin and C-peptide levels. RESULTS: Obese youths with 1hPG ≥7.4 mmol/L (or 133 mg/dL; n = 83) exhibited higher body mass index (BMI), plasma triglycerides and fasting and post-load glucose concentrations than individuals with 1hPG <7.4 mmol/L. Also, 1hPG ≥7.4 mmol/L was associated with a lower disposition index (DI) (P < 0.0001) and with alterations in whole-body insulin sensitivity, ß-cell function and insulin clearance. Adolescents with 1hPG ≥7.4 mmol/L were approximately three times more likely to develop prediabetes (ie, impaired glucose tolerance and/or impaired fasting glucose) over time (OR, 2.92 [1.22-6.98]; P = 0.02), independent of age, sex, race/ethnicity, BMI, insulin sensitivity, DI and plasma glucose concentrations. No differences emerged in the risk of prediabetes related to 1-hour hyperglycaemia among different ethnic groups. CONCLUSIONS: A plasma glucose concentration ≥ 7.4 mmol/L at 1 hour during an OGTT is associated with a worse clinical and metabolic phenotype and may be an independent predictor of progression to prediabetes in obese youths with NGT.

Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population.

OBJECTIVES: The risk of early-onset type 2 diabetes associated with the severity of obesity in youth is not well understood. This study aims to determine metabolic alterations and type 2 diabetes risk among American Indian children who are obese or severely obese. METHODS: Incidence rates of diabetes before 20 years (youth-onset) and 45 years were computed in 2728 children who were from 5 to <10 years and 4317 adolescents who were from 10 to <18 years without diabetes examined between 1965 and 2007. Obesity was defined as age-sex-adjusted body mass index (BMI) ≥95th percentile, and its severity was quantified as the percentage of the 95th percentile (%BMIp95 ). RESULTS: In the younger cohort, 0.9% of those non-obese and 2.9% of those with 100% to <120%BMIp95 had impaired glucose tolerance (IGT) compared to 8.6% of those with ≥140%BMIp95 . In the older cohort, 2.9% of those non-obese and 9.8% of those with 100% to <120%BMIp95 had IGT compared to 13.3% of those with ≥160%BMIp95 . The incidence of youth-onset diabetes was 3.8 and 4.9/1000 person-years in the child and adolescent cohorts, respectively, and before the age of 45 was 12.3 and 16.8/1000 person-years, respectively. Incidence rates of youth-onset diabetes in those with the most severe obesity (≥140%BMIp95 ) were 2.3 to 5.1 times as high as in those with the least severe obesity (100 to <120%BMIp95 ), and for onset of diabetes before the age of 45 were 1.6 to 2.2 times as high. CONCLUSIONS: Severe obesity in an American Indian population is a major driver of type 2 diabetes developing in adolescents and young adults.

Impact of adopting the 2013 World Health Organization criteria for diagnosis of gestational diabetes in a multi-ethnic Asian cohort: a prospective study.

BACKGROUND: We assessed the impact of adopting the 2013 World Health Organization (WHO) diagnostic criteria on the rates of gestational diabetes (GDM), pregnancy outcomes and identification of women at future risk of type 2 diabetes. METHODS: During a period when the 1999 WHO GDM criteria were in effect, pregnant women were universally screened using a one-step 75 g 2-h oral glucose tolerance test at 26-28 weeks' gestation. Women were retrospectively reclassified according to the 2013 criteria, but without the 1-h glycaemia measurement. Pregnancy outcomes and glucose tolerance at 4-5 years post-delivery were compared for women with GDM classified by the 1999 criteria alone, GDM by the 2013 criteria alone, GDM by both criteria and without GDM by both sets of criteria. RESULTS: Of 1092 women, 204 (18.7%) and 142 (13.0%) were diagnosed with GDM by the 1999 and 2013 WHO criteria, respectively, with 27 (2.5%) reclassified to GDM and 89 (8.2%) reclassified to non-GDM when shifting from the 1999 to 2013 criteria. Compared to women without GDM by both criteria, cases reclassified to GDM by the 2013 criteria had an increased risk of neonatal jaundice requiring phototherapy (relative risk (RR) = 2.78, 95% confidence interval (CI) 1.32, 5.86); despite receiving treatment for GDM, cases reclassified to non-GDM by the 2013 criteria had higher risks of prematurity (RR = 2.17, 95% CI 1.12, 4.24), neonatal hypoglycaemia (RR = 3.42, 95% CI 1.04, 11.29), jaundice requiring phototherapy (RR = 1.71, 95% CI 1.04, 2.82), and a higher rate of abnormal glucose tolerance at 4-5 years post-delivery (RR = 3.39, 95% CI 2.30, 5.00). CONCLUSIONS: Adoption of the 2013 WHO criteria, without the 1-h glycaemia measurement, reduced the GDM rate. Lowering the fasting glucose threshold identified women who might benefit from treatment, but raising the 2-h threshold may fail to identify women at increased risk of adverse pregnancy and future metabolic outcomes. TRIAL REGISTRATION: NCT01174875 . Registered 1 July 2010 (retrospectively registered).

A comparison of the genetic and clinical risk factors for arterial hypertension between indigenous and non-indigenous people of the Shoria Mountain Region.

BACKGROUND: This study investigated the non-genetic and genetic risk factors for arterial hypertension (AH) in two ethnic groups living in the Mountain Shoria region: Shors and non-indigenous people. METHODS: Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older). RESULTS: The prevalence of AH was lower in Shors (39.9% vs. 46.1%), mainly due to differences between men from the different groups: 33.2% vs. 45.8%. The percentage of people with AH, overweight, and obesity (including transabdominal obesity) in the different age groups did not differ between ethnicities. We identified statistically significant differences in the prevalence of hypertension according the two ethic groups according to age, body weight, and abdominal obesity. I/D ACE and ADRA2B polymorphisms were associated with AH. In DD ACE and DD ADRA2B carriers, there were fewer hypertensive patients in Shors than in non-indigenous people: 40.6% vs. 58.6% and 38.3% vs. 64.0%, respectively. In DD ACE carriers, more Shors had AH (60.0% vs. 37.1%). CONCLUSION: Among Shors, the following factors increased AH risk: female sex, age, hypercholesterolemia, hyperbetacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), glucose intolerance, and the DD ACE, CT MTHFR, and AA ADRB1 genotypes; among the non-indigenous population, the main factors were age, hypercholesterolemia, hyperbetacholesterinemia, hypoalfacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), and ID ACE genotype.

Adult height and glucose tolerance: a re-appraisal of the importance of body mass index.

AIM: To study both the association between adult height and glucose regulation based on findings from a 75-g oral glucose tolerance test, and the combined effect of height and adiposity on glucose values. METHODS: We conducted a population-based, cross-sectional study among apparently healthy people with high cardiovascular risk living in south-western Finland. The study included 2659 participants aged 45-70 years, who had at least one cardiovascular risk factor but no previously diagnosed diabetes or manifested cardiovascular disease. An oral glucose tolerance test was performed in all participants. Height and weight were measured and BMI was calculated. The participants were divided into five height groups based on normal distribution. For further analysis of the association between height and glucose concentrations the participants were divided into four BMI groups (<25.0 kg/m2 ; 25-29.9 kg/m2 ; 30-34.9 kg/m2 ; ≥35 kg/m2 ). Data were analysed using age-adjusted linear regression models. RESULTS: Height was inversely associated with 2-h plasma glucose, but not with fasting plasma glucose concentration. No gender difference was observed. The 2-h plasma glucose values increased with an increase in BMI, so that height was inversely associated with 2-h plasma glucose in the three lowest BMI groups, but not in the highest BMI group (P=0.33). CONCLUSIONS: Taller people had lower 2-h plasma glucose concentrations than shorter people, up to a BMI of 35 kg/m2 . Adjustment for height and BMI is needed for accurate interpretation of oral glucose tolerance tests.

Conversion of gestational diabetes mellitus to future Type 2 diabetes mellitus and the predictive value of HbA1c in an Indian cohort.

AIM: To investigate the distribution of and risk factors for dysglycaemia (Type 2 diabetes and prediabetes) in women with previous gestational diabetes mellitus in India. METHODS: All women (n = 989) from two obstetric units in New Delhi and Hyderabad with a history of gestational diabetes were invited to participate, of whom 366 (37%) agreed. Sociodemographic, medical and anthropometric data were collected and 75-g oral glucose tolerance test were carried out. RESULTS: Within 5 years (median 14 months) of the pregnancy in which they were diagnosed with gestational diabetes, 263 (72%) women were dysglycaemic, including 119 (32%) and 144 (40%) with Type 2 diabetes and prediabetes, respectively. A higher BMI [odds ratio 1.16 per 1-kg/m2 greater BMI (95% CI 1.10, 1.28)], presence of acanthosis nigricans [odds ratio 3.10, 95% CI (1.64, 5.87)], postpartum screening interval [odds ratio 1.02 per 1 month greater screening interval 95% CI (1.01, 1.04)] and age [odds ratio 1.10 per 1-year older age 95% CI (1.04, 1.16)] had a higher likelihood of having dysglycaemia. The American Diabetes Association-recommended threshold HbA1c value of ≥ 48 mmol/mol (6.5%) had a sensitivity and specificity of 81.4 and 90.7%, respectively, for determining the presence of Type 2 diabetes postpartum. CONCLUSION: The high post-pregnancy conversion rates of gestational diabetes to diabetes reported in the present study reinforce the need for mandatory postpartum screening and identification of strategies for preventing progression to Type 2 diabetes. Use of the American Diabetes Association-recommended HbA1c threshold for diabetes may lead to significant under-diagnosis.

Differences in ß-cell function and insulin secretion in Black vs. White obese adolescents: do incretin hormones play a role?

Black youth are at higher risk for type 2 diabetes (T2D) than their White peers. Previously we demonstrated that for the same degree of insulin sensitivity, Black youth have an upregulated ß-cell function and insulin hypersecretion, in response to intravenous (iv) glucose, compared with Whites. To investigate if the same holds true during an oral glucose challenge and because of the important role of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in augmenting insulin secretion, we examined ß-cell function and incretin hormones in 85 Black and 78 White obese adolescents, with normal glucose tolerance (NGT), during a 2-h oral glucose tolerance test (OGTT) with mathematical modeling of plasma glucose and C-peptide concentrations to assess ß-cell glucose sensitivity (ßCGS), rate sensitivity, potentiation factor, and insulin sensitivity. Incretin, pancreatic polypeptide, and glucagon concentrations were measured during the OGTT. Black obese youth had a heightened early insulin secretion together with significantly greater ßCGS, rate sensitivity, and potentiation factor compared with Whites, with no differences in incretin and glucagon concentrations. Basal and stimulated insulin clearance was lower (p = 0.001) in Black vs. White youth. In conclusion, during an OGTT Black obese youth with NGT demonstrate a pronounced early insulin secretion jointly with heightened ß-cell glucose sensitivity, rate sensitivity, and potentiation factor. These racial disparities in ß-cell function and the pathophysiological components of T2D are unlikely to be attributed to incretin hormones and remain to be investigated further to explain the metabolic basis for the enhanced risk of T2D in back youth.

[Application and improvement of Chinese Diabetes Risk Score on screening type 2 diabetes mellitus in Wuhai City, Inner Mongolia].

OBJECTIVE: To explore the application and improvement of "Chinese Diabetes Risk Score " on screening type 2 diabetes mellitus in Wuhai City, Inner Mongolia. METHODS: Using multi-stage systematic sampling, 6987 adults were selected to be administered questionnaire and to finish anthropological measurements( height, weight, waist circumference, and blood pressure) and blood tests for fasting plasma glucose and glycosylated hemoglobin. According to Chinese Diabetes Risk Score( DRS-1), some new lifestyle factors associated with diabetes risk were add to the construction of New Diabetes Risk Score( DRS-3). RESULTS: Multi-logistic regression analysis showed a statistically significant positive association between cereals intake and diabetes risk( P <0. 05). In contrast, consumption of fruits was significantly, inversely associated with diabetes risk after adjustment of potential confounders( P < 0. 05). The AUC of the newrisk score( DRS-3), which were constructed by cereals and fruits intake and some other factors, significantly higher when compared with the AUC of the original risk score( DRS-1)( 0. 770 and 0. 783, respectively). The sensitivity and specificity of DRS-1 were 85. 8% and 54. 0% respectively when using the cutoff value recommended( 25 scores). While the sensitivity and specificity of DRS-3 were 85. 5% and 57. 7% respectively when using the optimal cutoff value( 27 scores). CONCLUSION: Chinese Diabetes Risk Score can be used as a primary screening tool for diabetes, and it is necessary to include some lifestyle factors for the improvement of its screening ability.

Impact of lifestyle intervention in primary prevention of Type 2 diabetes did not differ by baseline age and BMI among Asian-Indian people with impaired glucose tolerance.

AIM: To investigate whether the effectiveness of lifestyle interventions on the incidence of diabetes was influenced by the baseline age and BMI of the Asian-Indian participants with prediabetes. METHODS: Pooled data, obtained from two of our Indian Diabetes Prevention Programmes (2006, n=236 and 2013, n=473; total N=709) which had similar baseline characteristics and intervention principles, were analysed. For the present secondary analysis we dichotomously categorized the participants' baseline age (<45 and ≥45 years) and BMI (<25.0 and ≥ 25.0 kg/m2 ). Glycaemic status was ascertained at 6-monthly intervals by oral glucose tolerance tests. The incidence rates of diabetes and relative risk reduction in both the intervention and the control group were calculated for categories of baseline age and BMI. Interactions between the intervention and baseline age and BMI on diabetes risk were also analysed. RESULTS: Incident diabetes was diagnosed in 227 of the total 709 participants (32.0%) [control group 139 participants (38.8%) vs intervention group 88 participants (24.2%)] during the median follow-up period of 2 years. The overall relative risk reduction was 35.4% (95% CI 19.3-48.3). Lifestyle intervention was equally effective in both age groups [relative risk reduction in those aged <45 years: 43.7% (95% CI 19.8-60.5) and in those aged ≥ 45 years: 28.9% (95% CI 5.3-46.6) P for interaction = 0.52] and in categories of BMI [BMI <25 kg/m2 : 36.1% (95% CI 9.5-54.9); and BMI ≥ 25 kg/m2 : 34.8% (95% CI 12.9-51.2); P for interaction = 0.95]. CONCLUSIONS: In Asian-Indian individuals with prediabetes, the effectiveness of lifestyle intervention was not modified by baseline age and BMI.

Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin.

AIMS: We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South Asian origin. METHODS: For 682 European and 520 South Asian men and women, aged 58-85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. RESULTS: Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist-hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c -defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c -defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. CONCLUSIONS: Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European group. These findings have implications for screening, and early cardiovascular prevention strategies in South Asian populations.

One-hour plasma glucose as a predictor of the development of Type 2 diabetes in Japanese adults.

AIMS: To test the hypothesis that 1-h plasma glucose in an oral glucose tolerance test is a better predictor of the development of diabetes than 2-h plasma glucose, independently of indices of insulin secretion or action in Japanese adults. METHODS: A historical cohort study was conducted in 1445 Japanese workers who did not have diabetes. The association between 1-h plasma glucose and the development of Type 2 diabetes was analysed. RESULTS: Overall, 95 of the study participants developed Type 2 diabetes during a mean follow-up of 4.5 years. The area under the receiver-operating characteristic curve for 1-h plasma glucose for future diabetes [0.88 (95% CI 0.84-0.91)] was greater than that for 2-h plasma glucose [0.79 (95% CI 0.74-0.84)], and for insulinogenic [0.73 (95% CI 0.68-0.78)] and disposition indices [0.79 (95% CI 0.74-0.84); P < 0.05]. Compared with the first quartile, the hazard ratio for future diabetes in the fourth quartile of 1-h plasma glucose was 42.5 [95% CI 5.7-315.2 (P < 0.05)] and the hazard ratio in the fourth quartile of 2-h plasma glucose was 4.4 [95% CI 1.8-10.8 (P < 0.05)], after adjustments for covariates including fasting plasma glucose. The significance of the elevated hazard ratio in the fourth quartile of 1-h plasma glucose was maintained after adjustments for 2-h plasma glucose, insulinogenic index or disposition index, whereas the elevation of the hazard ratio in the fourth quartile of 2-h plasma glucose was diminished and was no longer significant after adjustments for 1-h plasma glucose. CONCLUSIONS: One-hour plasma glucose had a greater association with the future development of Type 2 diabetes than did 2-h plasma glucose, independently of oral glucose tolerance test-derived indices of insulin action in a Japanese population.

High protein and cholesterol intakes associated with emergence of glucose intolerance in a low-risk Canadian Inuit population.

OBJECTIVE: The rate of type 2 diabetes mellitus among Inuit is 12·2 % in individuals over 50 years of age, similar to the Canadian prevalence. Given marked dietary transitions in the Arctic, we evaluated the dietary and other correlates of not previously diagnosed glucose intolerance, defined as type 2 diabetes mellitus, impaired fasting glucose or impaired glucose tolerance. DESIGN: Cross-sectional analyses were limited to adults with a completed 2 h oral glucose tolerance test and without pre-existing diabetes. Anthropometric assessments, health and medication usage questionnaires and a 24 h dietary recall were administered. SETTING: Canadian International Polar Year Inuit Health Survey (2007-2008). SUBJECTS: Inuit adults (n 777). RESULTS: Glucose intolerance was associated with older age and adiposity. Percentage of energy from protein above the Acceptable Macronutrient Distribution Range of 35 %, compared with intake within the range, was associated with increased odds of glucose intolerance (OR=1·98; 95 % CI 1·09, 3·61) in multivariable analyses. Further, cholesterol intake in the highest three quartiles combined (median exposures of 207, 416 and 778 mg/d, respectively) compared with the lowest quartile (median intake of 81 mg/d) was associated with glucose intolerance (OR=2·15; 95 % CI 1·23, 3·78) in multivariable analyses. Past-day traditional food consumption was borderline protective of glucose intolerance (P=0·054) and high fibre intake was not significantly protective (P=0·08). CONCLUSIONS: The results contribute to the existing literature on high protein and cholesterol intakes as they may relate to diabetes risk.

Outreach to diversify clinical trial participation: A randomized recruitment study.

BACKGROUND/AIMS: Racial and ethnic minorities remain underrepresented in clinical research, yet few recruitment strategies have been rigorously evaluated. METHODS: We experimentally tested whether targeted recruitment letters acknowledging diabetes health disparities and health risks specific to recipients' racial/ethnic group improved two metrics of trial participation: willingness to be screened and enrollment. This experiment was efficiently nested within a randomized clinical trial examining a preventive lifestyle intervention among women at high risk for diabetes. Pregnant women with gestational diabetes or impaired glucose tolerance (N = 445) were randomized to receive a targeted recruitment letter with health risk information specific to their racial/ethnic group (n = 216), or a standard letter with risk information for the general population (n = 229). All letters were bilingual in English and Spanish. RESULTS: The targeted as compared to the standard letter did not improve screening or enrollment rates overall or within separate racial/ethnic groups. Among Latina women who preferred Spanish, the targeted letter showed trends for improved screening (66.7% vs 33.3%, p = .06) and enrollment rates (38.9% vs 13.3%, p = .13). In contrast, among Latina women who preferred English, the targeted letter significantly lowered screening (29.6% vs 57.1%, p = .04) and showed trends for lowered enrollment rates (25.9% vs 50.0%, p = .07). CONCLUSION: Results from this randomized study appear to suggest that recruitment letters with diabetes health risk information targeted to recipients' race/ethnicity may improve one metric of clinical trial participation among Latina women who prefer Spanish, but not English. Larger experimental studies, incorporating input from diverse participant stakeholders, are needed to develop evidence-based minority recruitment strategies.

Impact of variants of the EXT2 gene on Type 2 diabetes and its related traits in the Chinese han population.

PURPOSE/AIM OF THE STUDY: Exostosin 2 (EXT2) is involved in early pancreatic development and the regulation of insulin synthesis. In this study, we aim to evaluate the contribution of EXT2 to the genetic pathogenesis of type 2 diabetes and its related traits in the Chinese population. MATERIALS AND METHODS: A case-control study in a Chinese Han population was conducted that included 4766 patients with type 2 diabetes and 4596 control subjects from 14 different regions of China. Three single nucleotide polymorphism (SNP), rs3740878, rs11037909 and rs1113132, in the EXT2 gene were genotyped using the Illumina GoldenGate Genotyping assay. RESULTS: After adjusting for sex, age and body mass index, logistic regression analysis revealed that the EXT2 gene had no association with type 2 diabetes using an additive genetic model [rs3740878 (Odds Ratio (OR) = 0.996, 95% confidence interval (CI) 0.928-1.069, p = 0.910), rs11037909 (OR = 1.003, 95%CI 0.933-1.078, p = 0.931), and rs1113132 (OR = 0.993, 95% CI 0.925-1.065, p = 0.842)]. None of these SNPs were associated with beta cell function as determined using the baseline disposition index, early phase insulin secretion and Oral Glucose Tolerance Test (OGTT) total disposition index. CONCLUSIONS: Our study suggests that the EXT2 gene might not have a major role in the development of type 2 diabetes in the Chinese population.

Osteocalcin is inversely associated with glucose levels in middle-aged Tibetan men with different degrees of glucose tolerance.

BACKGROUND: Research on the characteristics and mechanisms of diabetes in Tibetans is scant. Especially, there is no study on the relationship between osteocalcin and glucose metabolism. The objective of this study was to investigate the associations of serum total osteocalcin (tOC) and undercarboxylated osteocalcin (ucOC) with glucose and lipid metabolism in Chinese indigenous Tibetans with different degrees of glucose tolerance. METHODS: In this study, 160 middle-aged Tibetan men were involved, including 46 subjects with normal glucose tolerance (NGT), 52 subjects with impaired glucose regulation (IGR) and 62 subjects with type 2 diabetes. The homeostasis model assessment (HOMA) parameters, including HOMA-IR and HOMA-B, were used to estimate insulin resistance and ß-cell function, respectively. Adiponectin, leptin, testosterone, 1,25-dihydroxyvitamin D, tOC and ucOC were measured using ELISA kits. RESULTS: After adjustment for age and body mass index, plasma tOC level was correlated negatively with fasting and 30-min post-OGTT glucose, HOMA-IR, leptin and testosterone; plasma ucOC level was correlated negatively with 30-min post-OGTT glucose, total cholesterol and 1,25-dihydroxyvitamin D; ucOC : tOC was correlated positively with leptin. The negative association between HOMA-IR and tOC remained significant after correcting for adiponectin; however, the association disappeared after correcting for leptin. HOMA-IR was correlated negatively with age, adiponectin and tOC, and positively with total cholesterol, triglyceride and leptin. Stepwise linear regression analysis revealed that total cholesterol, leptin and adiponectin were independent predictors for HOMA-IR in all subjects. CONCLUSIONS: Our data support a link between osteocalcin and glucose metabolism in middle-aged Tibetan men. The improved glucose tolerance exerted by tOC may be related to improved insulin sensitivity rather than improved ß-cell function.

Evidence for threshold effects of 25-hydroxyvitamin D on glucose tolerance and insulin resistance in black and white obese postmenopausal women.

We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone-related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose-insulin metabolism such that 25(OH)D ≥ ∼26 µg/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at clinicaltrials.gov as NCT01798030.

Estudio Parto: postpartum diabetes prevention program for hispanic women with abnormal glucose tolerance in pregnancy: a randomised controlled trial - study protocol.

BACKGROUND: Diabetes and obesity have reached epidemic proportions in the U.S. with rates consistently higher among Hispanics as compared to non-Hispanic whites. Among Hispanic women diagnosed with gestational diabetes mellitus (GDM), 50% will go on to develop type 2 diabetes within 5 years of the index pregnancy. Although randomised controlled trials among adults with impaired glucose tolerance have shown that diet and physical activity reduce the risk of type 2 diabetes, such programs have not been tested in high-risk postpartum women. The overall goal of this randomised controlled trial is to test the efficacy of a culturally and linguistically modified, individually-tailored lifestyle intervention to reduce risk factors for type 2 diabetes and cardiovascular disease among postpartum Hispanic women with a history of abnormal glucose tolerance during pregnancy. METHODS/DESIGN: Hispanic pregnant women who screen positive for GDM will be recruited and randomly assigned to a Lifestyle Intervention (n = 150) or a Health & Wellness (control) Intervention (n = 150). Multimodal contacts (i.e., in-person, telephone, and mailed materials) will be used to deliver the intervention from late pregnancy (29 weeks gestation) to 12 months postpartum. Targets of the intervention are to achieve Institute of Medicine Guidelines for postpartum weight loss; American Congress of Obstetrician and Gynecologist guidelines for physical activity; and American Diabetes Association guidelines for diet. The intervention draws from Social Cognitive Theory and the Transtheoretical Model and addresses the specific cultural and environmental challenges faced by low-income Hispanic women. Assessments will be conducted at enrollment, and at 6-weeks, 6-months, and 12-months postpartum by trained bicultural and bilingual personnel blinded to the intervention arm. Efficacy will be assessed via postpartum weight loss and biomarkers of insulin resistance and cardiovascular risk. Changes in physical activity and diet will be measured via 7-day actigraph data and three unannounced 24-hour dietary recalls at each assessment time period. DISCUSSION: Hispanic women are the fastest growing minority group in the U.S. and have the highest rates of sedentary behavior and postpartum diabetes after a diagnosis of GDM. This randomised trial uses a high-reach, low-cost strategy that can readily be translated into clinical practice in underserved and minority populations. TRIAL REGISTRATION: NCT01679210.

Dietary patterns in Greenland and their relationship with type 2 diabetes mellitus and glucose intolerance.

OBJECTIVE: Traditional Inuit dietary patterns have been found to be beneficial for CVD but have not been investigated in relation to glucose intolerance. We examined the association between dietary patterns and type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). DESIGN: Cross-sectional design with a priori derived dietary patterns from an FFQ resulted in five patterns: imported meat (n 196), traditional food (n 601), balanced diet (n 126), unhealthy diet (n 652) and standard diet (n 799). SETTING: Associations between dietary patterns and glucose-related outcomes were tested by linear and logistic regression analyses. Data included: dietary intake by FFQ, waist circumference, ethnicity, frequency of alcohol intake and smoking, physical activity, and oral glucose tolerance test results. Fasting participants and those without diagnosed T2DM were classified into normal glucose tolerance, IGT, IFG or T2DM. HOMA-IR (homeostatic model assessment-insulin resistance index) and HOMA-ß (homeostatic model assessment of ß-cell function) were calculated. SUBJECTS: Data included 2374 Inuit, aged 18+ years. RESULTS: Participants with a traditional dietary pattern had higher fasting plasma glucose (mean 5·73 (95% CI 5·68, 5·78) mmol/l, P < 0·0001) and lowest HOMA-ß (48·66 (95% CI 46·86, 50·40), P < 0·0001). The traditional diet gave significantly higher odds for IFG and T2DM than the balanced diet, imported meat diet, standard diet and unhealthy diet. CONCLUSIONS: Traditional food was positively associated with T2DM, IFG and fasting plasma glucose, and negatively associated with ß-cell function, compared with a standard diet. The imported meat diet seemed the best in relation to glucose intolerance, with lowest fasting plasma glucose and lowest odds for IFG and T2DM.