A high amount of subcutaneous fat is suggested to explain the observation of lower obesity-associated metabolic risk among Inuit than among Europeans. We examined the association between measures of ...obesity (visceral adipose tissue VAT, subcutaneous adipose tissue SAT, BMI, waist circumference WC, and percentage of body fat) and the indices of glucose metabolism (fasting and 2-h glucose levels, insulin resistance per homeostasis model assessment HOMA-IR, and the insulin sensitivity index ISI0,120) among Greenland Inuit.
A total of 3,108 adult Inuit participated in a population-based study. The examination included a 75-g oral glucose tolerance test and anthropometric measurements. VAT and SAT were measured by ultrasound according to a validated protocol. Information on sociodemographic characteristics and health behaviors was obtained by interview.
Mean SATs were 1.8 and 3.5 cm in men and women, respectively. Mean VATs were 7.0 and 6.3 cm in men and women, respectively. The total prevalence of type 2 diabetes was 9%. Percentage of body fat generally was most strongly associated with all outcomes. Both SAT and VAT were significantly associated with glucose intolerance, fasting and 2-h plasma glucose levels, HOMA-IR, and ISI0,120. VAT was more strongly associated with all outcomes than was SAT. After further adjustment for BMI or WC, VAT was associated with glucose intolerance and insulin resistance, whereas there was a trend toward a negative or no association with SAT.
High mean values of SAT may to a large extent explain the high WC in Inuit populations, and this is suggested to contribute to the lower observed metabolic risk for a given level of obesity.
OBJECTIVE To compare screen-detected diabetes prevalence and the degree of diagnostic agreement by ethnicity with the current oral glucose tolerance test (OGTT)-based and newly proposed A1C-based ...diagnostic criteria. RESEARCH DESIGN AND METHODS Six studies (1999-2009) from Denmark, the U.K., Australia, Greenland, Kenya, and India were tested for the probability of an A1C > or =6.5% among diabetic case subjects based on an OGTT. The difference in probability between centers was analyzed by logistic regression adjusting for relevant confounders. RESULTS Diabetes prevalence was lower with the A1C-based diagnostic criteria in four of six studies. The probability of an A1C > or =6.5% among OGTT-diagnosed case subjects ranged widely (17.0-78.0%) by study center. Differences in diagnostic agreement between ethnic subgroups in the U.K. study were of the same magnitude as between-country comparisons. CONCLUSIONS A shift to an A1C-based diagnosis for diabetes will have substantially different consequences for diabetes prevalence across ethnic groups and populations.
We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of ...17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapBT2D, to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Various strategies have been used to induce lifestyle changes to reduce ischaemic heart disease (IHD) with various successes. The aim of Inter99 is to assess the effect on IHD incidence of ...individually tailored non-pharmacological intervention on lifestyle using a newly developed computer-based health educational tool. The article describes the study and baseline results.
From a population of 61,301 individuals two random samples (high intensity intervention group (A), n = 11,708; low intensity intervention group (B), n = 1308) are screened to assess their absolute risk of IHD. Those at high risk receive individual lifestyle counselling. Individuals in group A are furthermore offered lifestyle counselling in groups on smoking cessation or physical activity/diet over a 6-month period. Individuals in group B are referred to their GP. High-risk persons are re-counselled after 1 and 3 years and the whole group is re-invited after 5 years. The remaining 48,285 (group C) are followed by questionnaire. The total population is followed through central registers. Intermediate end-points are changes in lifestyle, cholesterol, blood pressure and body mass index. Final end-point is reduction in incidence of IHD.
The randomization leads to comparable groups. Participation rate was 52.5%. A total of 60% fulfilled the predetermined criteria for being at high risk for developing IHD. After an individual lifestyle counselling 41% accepted group-based counselling.
This large randomized population based trial discloses a noticeable need for and acceptance of lifestyle intervention in the general population.
Association Testing of Novel Type 2 Diabetes Risk Alleles in the JAZF1 , CDC123 / CAMK1D , TSPAN8 , THADA , ADAMTS9 , and NOTCH2 Loci With Insulin Release, Insulin Sensitivity, and Obesity in a ...Population-Based Sample of 4,516 Glucose-Tolerant Middle-Aged
Danes
Niels Grarup 1 ,
Gitte Andersen 1 ,
Nikolaj T. Krarup 1 ,
Anders Albrechtsen 2 ,
Ole Schmitz 3 4 ,
Torben Jørgensen 5 ,
Knut Borch-Johnsen 1 5 6 ,
Torben Hansen 1 and
Oluf Pedersen 1 6
1 Steno Diabetes Center, Copenhagen, Denmark
2 Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
3 Department of Endocrinology and Diabetes, Aarhus University Hospital, Aarhus, Denmark
4 Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark
5 Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
6 Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
Corresponding author: Niels Grarup, ngrp{at}steno.dk
Abstract
OBJECTIVE— We evaluated the impact on diabetes-related intermediary traits of common novel type 2 diabetes–associated variants in the
JAZF1 (rs864745), CDC123 / CAMK1D (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), AD AMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of genome-wide association data.
RESEARCH DESIGN AND METHODS— We genotyped the six variants in 4,516 middle-aged glucose-tolerant individuals of the population-based Inter99 cohort who
were all characterized by an oral glucose tolerance test (OGTT).
RESULTS— Homozygous carriers of the minor diabetes risk G-allele of the CDC123 / CAMK1D rs12779790 showed an 18% decrease in insulinogenic index (95% CI 10–27%; P = 4 × 10 −5 ), an 18% decrease in corrected insulin response (CIR) (8.1–29%; P = 4 × 10 −4 ), and a 13% decrease in the ratio of area under the serum-insulin and plasma-glucose curves during an OGTT (AUC-insulin/AUC-glucose)
(5.8–20%; P = 4 × 10 −4 ). Carriers of the diabetes-associated T-allele of JAZF1 rs864745 had an allele-dependent 3% decrease in BIGTT-AIR (0.9–4.3%; P = 0.003). Furthermore, the diabetes-associated C-allele of TSPAN8 rs7961581 associated with decreased levels of CIR (4.5% 0.5–8.4; P = 0.03), of AUC-insulin/AUC-glucose ratio (3.9% 1.2–6.7; P = 0.005), and of the insulinogenic index (5.2% 1.9–8.6; P = 0.002). No association with traits of insulin release or insulin action was observed for the THADA , ADAMTS9 , or NOTCH2 variants.
CONCLUSIONS— If replicated, our data suggest that type 2 diabetes at-risk alleles in the JAZF1 , CDC123 / CAMK1D , and TSPAN8 loci associate with various OGTT-based surrogate measures of insulin release, emphasizing the contribution of abnormal pancreatic
β-cell function in the pathogenesis of type 2 diabetes.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 20 June 2008.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted June 16, 2008.
Received March 30, 2008.
DIABETES
Risk Scores for Type 2 Diabetes Can Be Applied in Some Populations but Not All
Charlotte Glümer , MD, PHD 1 ,
Dorte Vistisen , MSC, PHD 1 ,
Knut Borch-Johnsen , DMSC 1 ,
Stephen Colagiuri , MD 2 and
...on behalf of the DETECT-2 Collaboration
1 Steno Diabetes Center, Gentofte, Denmark
2 Department of Endocrinology and Diabetes, Prince of Wales Hospital, Sydney, Australia
Address correspondence and reprint requests to Charlotte Glümer, MD, PhD, Steno Diabetes Center, Niels Steensens Vej 2, 2820
Gentofte, Denmark. E-mail: chgl{at}steno.dk
Abstract
OBJECTIVE —Risk scores based on phenotypic characteristics to identify individuals at high risk of having undiagnosed diabetes have
been developed in Caucasian populations. The impact of known risk factors on having undiagnosed type 2 diabetes differs between
populations from different ethnic origin, and risk scores developed in Caucasians may not be applicable to other ethnic groups.
This study evaluated the performance of one risk score in nine populations of diverse ethnic origin.
RESEARCH DESIGN AND METHODS —Data provided by centers from around the world to the DETECT-2 project were used. The database includes population-based
surveys with information on at least 500 people without known diabetes having a 75-g oral glucose tolerance test. To date,
52 centers have contributed data on 190,000 individuals from 34 countries. In this analysis, nine cross-sectional studies
were selected representing diverse ethnic and regional backgrounds. The risk score assessed uses information on age, sex,
blood pressure treatment, and BMI.
RESULTS —This analysis included 29,758 individuals; 1,805 individuals had undiagnosed diabetes. The performance of the risk score
varied widely, with sensitivity, specificity, and percentage needing further testing ranging between 12 and 57%, 72 and 93%,
and 2 and 25%, respectively, with the worse performance in non-Caucasian populations. This variation in performance was related
to differences in the association between prevalence of undiagnosed diabetes and components of the risk score.
CONCLUSIONS —A typical risk score developed in Caucasian populations cannot be applied to other populations of diverse ethnic origins.
AUC, area under the receiver-operator characteristic curve
NHANES III, Third National Health and Nutrition Examination Survey
ROC, receiver-operator characteristic
RPM, Rotterdam Predictive Model
Footnotes
C.G. and K.B.-J. hold stock in and have received research funding from Novo Nordisk.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
Accepted October 28, 2005.
Received May 24, 2005.
DIABETES CARE
.
Purpose: Retinal vascular lesions such as microaneurysms and haemorrhages, while typical of diabetic retinopathy, are also seen in subjects without diabetes where they are associated with elevated ...cardiovascular mortality. In theory, these lesions could be a consequence of past hyperglycaemia. We examined the prevalence and risk factors for retinopathy, including lens fluorescence, a biomarker of cumulative life‐time glycaemia in adults without diabetes.
Methods: Cross‐sectional population‐based study of 711 subjects without diabetes (WHO 1999 criteria) aged 30–60 years, including oral glucose tolerance testing, clinical and laboratory examinations, non‐invasive ocular lens fluorometry and seven‐field fundus photography.
Results: Retinopathy was present in 8.3% (CI95 6.3–10.3%) of subjects. Higher systolic blood pressure (SBP) (p = 0.032), increasing body mass index (BMI) (p = 0.014) and wider waist circumference (p = 0.014) were significantly associated with retinopathy after adjusting for age and sex. Retinopathy was not significantly related to long‐term, short‐term or current glycaemia (lens fluorescence, HbA1c, fasting plasma glucose). In the multivariate analysis, the odds ratio (OR) for retinopathy in subjects with SBP ≥160 mmHg compared to subjects with SBP <130 mmHg was 2.68 (CI95 1.07–6.70, p = 0.036) and in subjects with BMI ≥30 compared to subjects with BMI < 25 the OR for retinopathy was 2.14 (CI95 1.01–4.57, p = 0.049) when adjusting for both variables, age, sex, the presence of impaired glucose tolerance and impaired fasting glucose.
Conclusion: Retinopathy in subjects without diabetes was associated with hypertension and obesity. The study found no evidence that microvascular retinopathy in non‐diabetic subjects was a consequence of past hyperglycaemia.
Context: The type 2 iodothyronine deiodinase (D2) catalyzes the conversion of T4 to the active form of thyroid hormone, which is a critical regulator of thermogenesis and glucose metabolism. A ...Thr92Ala polymorphism in the gene encoding D2 (DIO2) has been reported to associate with insulin resistance.
Objective: The aim of the present study was to assess the impact of the DIO2 Thr92Ala variant on type 2 diabetes (T2D), obesity, and related quantitative metabolic traits including measures of insulin resistance. Because DIO2 is activated through a β-adrenergic receptor-dependent pathway, we further hypothesized that variation in the ADRB genes interacts with DIO2 Thr92Ala variant to influence metabolic traits.
Design and Patients: The DIO2 polymorphism was genotyped in a total of 7342 white subjects including 1405 T2D patients.
Results: We detected no significant association of the DIO2 Thr92Ala polymorphism with T2D or obesity. We observed nominal significant associations of genotype with increased area under the serum insulin curve during an oral glucose tolerance test (P = 0.03) and elevated fasting plasma glucose (P = 0.02) in homozygous Ala92 allele carriers, the latter strengthened by epistasis with the ADRB2 Gly16Arg variant in a double recessive model (P = 0.004). However, after permutation procedure, performed to correct for multiple hypothesis testing, the associations did not reach study-wide significance.
Conclusions: The DIO2 Thr92Ala variant does not confer an increased risk of T2D, obesity, or insulin resistance.
Aims/Hypothesis
The relationships between smoking and glycaemic variables have not been well explored. We compared HbA
1c
, fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex- ...and never-smokers.
Methods
This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies. Means of three glycaemic variables in current, ex- and never-smokers were modelled by linear regression, with study as a random factor. The
I
2
statistic was used to evaluate heterogeneity among studies.
Results
HbA
1c
was 0.10% (95% CI 0.08, 0.12) (1.1 mmol/mol 0.9, 1.3) higher in current smokers and 0.03% (0.01, 0.05) (0.3 mmol/mol 0.1, 0.5) higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current and never-smokers (−0.004 mmol/l −0.03, 0.02) but FPG was higher in ex-smokers (0.12 mmol/l 0.09, 0.14). In comparison with never-smokers, 2H-PG was lower (−0.44 mmol/l −0.52, −0.37) in current smokers, with no difference for ex-smokers (0.02 mmol/l −0.06, 0.09). There was a large and unexplained heterogeneity among studies, with
I
2
always above 50%;
I
2
was little changed after stratification by sex and adjustment for age and BMI. In this study population, current smokers had a prevalence of diabetes that was 1.30% higher as screened by HbA
1c
and 0.52% lower as screened by 2H-PG, in comparison with never-smokers.
Conclusion/interpretation
Across this heterogeneous group of studies, current smokers had a higher HbA
1c
and lower 2H-PG than never-smokers. This will affect the chances of smokers being diagnosed with diabetes.
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