Objective: We aimed to examine the association between gestational diabetes mellitus (GDM) and 11 recently identified type 2 diabetes susceptibility loci.
Research Design and Methods: Type 2 diabetes ...risk variants in TCF7L2, CDKAL1, SLC30A8, HHEX/IDE, CDKN2A/2B, IGF2BP2, FTO, TCF2, PPARG, KCNJ11, and WFS1 loci were genotyped in a cohort of women with a history of GDM (n = 283) and glucose-tolerant women of the population-based Inter99 cohort (n = 2446).
Results: All the risk alleles in the 11 examined type 2 diabetes risk variants showed an odds ratio (OR) greater than 1 for the GDM group compared with the control group ranging from 1.13 95% confidence interval (CI) 0.88–1.46 to 1.44 (95% CI 1.19–1.74) except for the WFS1 rs10010131 variant with OR 0.87 (95% CI 0.73–1.05). Combined analysis of all 11 variants showed a highly significant additive effect of multiple risk alleles on risk of GDM OR 1.18 (95% CI 1.10–1.27) per risk allele, P = 3.2 × 10−6). Applying receiver-operating characteristic showed an area under the receiver-operating characteristic curve of 0.62 for the genetic test alone and 0.73 when combining information on age, body mass index, and genotypes of the 11 gene variants.
Conclusions: The prevalence in a prior GDM group of several previously proven type 2 diabetes risk alleles equals the findings from association studies on type 2 diabetes. This supports the hypothesis that GDM and type 2 diabetes are two of the same entity.
The association among several type 2 diabetes risk variants with gestational diabetes mellitus points to identical geneticbackground for the two diseases.
OBJECTIVE
There is limited evidence on how intensive multifactorial treatment (IT) improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in ...routine clinical practice. We examined the effects of early detection and IT of type 2 diabetes in primary care on the prevalence of diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) 6 years later in a pragmatic, cluster-randomized parallel group trial.
RESEARCH DESIGN AND METHODS
A stepwise screening program in 190 general practices in Denmark was used to identify 1,533 people with type 2 diabetes. General practices were randomized to deliver either IT or routine care (RC) as recommended through national guidelines. Participants were followed for 6 years and measures of DPN and PAD were applied.
RESULTS
We found no statistically significant effect of IT on the prevalence of DPN and PAD compared with RC. The prevalence of an ankle brachial index ≤0.9 was 9.1% (95% CI 6.0–12.2) in the RC arm and 7.3% (5.0–9.6) in the IT arm. In participants tested for vibration detection threshold and light touch sensation, the prevalence of a least one abnormal test was 34.8% (26.7–43.0) in the RC arm and 30.1% (24.1–36.1) in the IT arm.
CONCLUSIONS
In a population with screen-detected type 2 diabetes, we did not find that screening followed by IT led to a statistically significant difference in the prevalence of DPN and PAD 6 years after diagnosis. However, treatment levels were high in both groups.
The aim of this study was to assess the level of urinary albumin excretion (microalbuminuria), which is associated with increased risk of coronary heart disease and death, in the population. ...Microalbuminuria has been suggested as an atherosclerotic risk factor. However, the lower cutoff level of urinary albumin excretion is unknown. It is also unknown whether impaired renal function confounds the association.
In the Third Copenhagen City Heart Study in 1992 to 1994, 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program, including a timed overnight urine sample. The participants were then followed up prospectively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death. During follow-up, 109 incident cases of coronary heart disease and 276 deaths were traced. A urinary albumin excretion above the upper quartile, ie, 4.8 microg/min, was associated with increased risk of coronary heart disease (RR, 2.0; 95% CI, 1.4 to 3.0; P<0.001) and death (RR, 1.9; 95% CI, 1.5 to 2.4; P<0.001) independently of age, sex, renal creatinine clearance, diabetes mellitus, hypertension, and plasma lipids. Lower levels of urinary albumin excretion were not associated with increased risk.
Microalbuminuria, defined as urinary albumin excretion >4.8 microg/min (corresponding to approximately 6.4 microg/min during daytime), is a strong and independent determinant of coronary heart disease and death. Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies.
Aims/hypothesis
Health check programmes for chronic disease have been introduced in a number of countries. However, there are few trials assessing the benefits and harms of these screening programmes ...at the population level. In a post hoc analysis, we evaluated the effect of population-based screening for type 2 diabetes and cardiovascular risk factors on mortality rates and cardiovascular events.
Methods
This register-based, non-randomised, controlled trial included men and women aged 40–69 years without known diabetes who were registered with a general practice in Denmark (
n
= 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk score questionnaire. Individuals at moderate-to-high risk were invited to visit their GP for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other general practices in Denmark constituted the retrospectively constructed no-screening (control) group. Outcomes were mortality rate and cardiovascular events (cardiovascular disease death, non-fatal ischaemic heart disease or stroke). The analysis was performed according to the intention-to-screen principle.
Results
Among the screening group, 27,177 (18%) individuals attended for assessment of diabetes status and cardiovascular risk. Of these, 1,533 were diagnosed with diabetes. During a median follow-up of 9.5 years, there were 11,826 deaths in the screening group and 141,719 in the no-screening group (HR 0.99 95% CI 0.96, 1.02,
p
= 0.66). There were 17,941 cardiovascular events in the screening group and 208,476 in the no-screening group (HR 0.99 0.96, 1.02,
p
= 0.49).
Conclusions/interpretation
A population-based stepwise screening programme for type 2 diabetes and cardiovascular risk factors among all middle-aged adults in Denmark was not associated with a reduction in rate of mortality or cardiovascular events between 2001 and 2012.
Background: Neuromedin U (NMU) is an anorexic neuropeptide expressed in the hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice overexpressing Nmu are hypophagic and lean.
...Objective: Our objective was to investigate whether variants in NMU are associated with human obesity.
Design: The coding region of NMU was analyzed for variants in obese Czech children and obese Danish adults. Identified missense variants were investigated for cosegregation with obesity in families or association with obesity in the general population.
Setting: The study was performed at Steno Diabetes Center, Denmark, and Department of Pediatrics, Charles University, Czech Republic.
Subjects and Methods: A total of 289 Czech children and adolescents with early-onset obesity and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean and unrelated Czech subjects.
Results: The rare NMU Arg165Trp variant cosegregated with childhood obesity in a Czech family. Homozygous carriers of the Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2–0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval, 0.7–1.1) among 3265 overweight and obese subjects (body mass index ≥ 25 kg/m2) odds ratio, 2.5 (1.2–5.3); P = 0.01.
Conclusion: Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.
Is the Current Definition for Diabetes Relevant to Mortality Risk From All Causes and Cardiovascular and Noncardiovascular
Diseases?
The DECODE Study Group and
on behalf of the European Diabetes ...Epidemiology Group
Abstract
OBJECTIVE —To assess the relation between fasting plasma glucose (FPG) or 2-h plasma glucose (2hPG) and mortality from all causes, cardiovascular
disease (CVD), and non-CVD and to determine whether the relationship is graded or threshold.
RESEARCH DESIGN AND METHODS —Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe (DECODE) is a collaborative prospective study
of 22 cohorts in Europe with baseline glucose measurements for 29,714 subjects aged 30–89 years who were followed-up for 11
years (329,050 person-years). Hazard ratio (HR) for death was estimated using Cox regression analysis.
RESULTS —High glucose concentrations as well as very low glucose levels were associated with increased risk of death. Compared with
an FPG of 4.50–6.09 mmol/l, the multivariate-adjusted HR (95% CI) for FPG <4.50 mmol/l was 1.2 (1.0–1.4) for all-cause, 1.3
(1.0–1.8) for CVD, and 1.1 (0.9–1.4) for non-CVD mortality; the corresponding HRs for diabetes (FPG ≥7.0 mmol/l) were 1.6
(1.4–1.8), 1.6 (1.3–1.9), and 1.6 (1.4–1.9), respectively. For a 2hPG of 3.01–4.50 mmol/l, as compared with a 2hPG of 4.51–5.50
mmol/l, the HRs were 1.1 (1.0–1.2), 1.1 (0.9–1.3), and 1.1 (1.0–1.3), respectively; the corresponding HRs for diabetes (2hPG
≥11.1 mmol/l) were 2.0 (1.7–2.3), 1.9 (1.5–2.4), and 2.1 (1.7–2.5), respectively. The HR for previously undetected diabetes
defined by 2hPG was not significantly different from that for known diabetes, which was significantly higher than that for
undetected diabetes based on FPG. Subjects with a 2hPG of 10.01–11.09 mmol/l had mortality risks similar to those diabetic
subjects defined by an FPG ≥7.0 mmol/l.
CONCLUSIONS —The relation between mortality and glucose was J shaped rather than showing threshold effect at high glucose levels, except
for CVD mortality and 2hPG, where the relation was graded and increasing.
2hPG, 2-h plasma glucose
CVD, cardiovascular disease
DECODE, Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe
FPG, fasting plasma glucose
HR, hazard ratio
IFG, impaired fasting glycemia
IGT, impaired glucose tolerance
Footnotes
Address correspondence and reprint requests to Dr. Qing Qiao, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology
and Health Promotion, National Public Health Institute, Mannerheimintie 166, KTTL, 6 krs, FIN-00300 Helsinki, Finland. E-mail:
qing.qiao{at}ktl.fi .
Received for publication 17 June 2002 and accepted in revised form 26 November 2002.
Members of the DECODE Study Group are listed in the appendix.
Additional information for this article can be found in an online appendix at http://care.diabetesjournals.org .
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
DIABETES CARE
BACKGROUND: The few studies examining the potential associations between glycemic index (GI), glycemic load (GL), and body mass index (BMI) have provided no clear pictures. Underreporting of energy ...intake may be one explanation for this. OBJECTIVE: We examined the associations between GI, GL, and BMI by focusing on the confounding factor of total energy intake and the effect of exclusion of low energy reporters (LERs). DESIGN: This was a cross-sectional study of 6334 subjects aged 30-60 y. Dietary intake was estimated from a food-frequency questionnaire. GI and GL were estimated by using white bread as the reference food. Underreporting of energy intake was assessed as reported energy intake divided by basal metabolic rate (EI/BMR); LERs were defined as those having an EI/BMR < 1.14. Univariate and multiple linear regression models were used to test for associations between GI, GL, and BMI. The confounders were sex, age, smoking, physical activity, alcohol intake, and energy intake. All analyses were conducted on 1) the entire population and 2) a subsample excluding LERs. RESULTS: In the univariate analyses of the entire population, GL was inversely associated with BMI. No association was observed for GI. After full adjustment (including energy intake), both GI and GL were positively associated with BMI. When LERs were excluded, GL was positively associated with BMI in all analyses, and GI was positively associated with BMI in the multiple analyses. CONCLUSIONS: We showed a positive association between GI, GL, and BMI. Energy adjustment and the exclusion of LERs significantly affected the results of the analysis; thus, we stress the importance of energy adjustment.
OBJECTIVE: There is limited evidence on how intensive multifactorial treatment (IT) improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in ...routine clinical practice. We examined the effects of early detection and IT of type 2 diabetes in primary care on the prevalence of diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) 6 years later in a pragmatic, cluster-randomized parallel group trial. RESEARCH DESIGN AND METHODS: A stepwise screening program in 190 general practices in Denmark was used to identify 1,533 people with type 2 diabetes. General practices were randomized to deliver either IT or routine care (RC) as recommended through national guidelines. Participants were followed for 6 years and measures of DPN and PAD were applied. RESULTS: We found no statistically significant effect of IT on the prevalence of DPN and PAD compared with RC. The prevalence of an ankle brachial index ≤0.9 was 9.1% (95% CI 6.0–12.2) in the RC arm and 7.3% (5.0–9.6) in the IT arm. In participants tested for vibration detection threshold and light touch sensation, the prevalence of a least one abnormal test was 34.8% (26.7–43.0) in the RC arm and 30.1% (24.1–36.1) in the IT arm. CONCLUSIONS: In a population with screen-detected type 2 diabetes, we did not find that screening followed by IT led to a statistically significant difference in the prevalence of DPN and PAD 6 years after diagnosis. However, treatment levels were high in both groups.
The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both ...variants. The aims of this study were to validate these obesity-associations through case-control studies and analyses of obesity-related quantitative traits. Moreover, since environmental and genetic factors may modulate the impact of a genetic variant, we wanted to perform such interaction analyses. We focused on physical activity as an environmental risk factor, and on the GWA identified obesity variants in FTO (rs9939609) and near MC4R (rs17782313) as genetic risk factors.
The four variants were genotyped in a combined study sample comprising a total of 18,014 subject ascertained from, the population-based Inter99 cohort (n = 6,514), the ADDITION screening cohort (n = 8,662), a population-based study sample (n = 680) and a type 2 diabetic patient group (n = 2,158) from Steno Diabetes Center.
No association with overweight, obesity or obesity-related measures was shown for either the INSIG2 rs7566605 or the PFKP rs6602024 variants. However, an interaction between the INSIG2 rs7566605 variant and the level of self-reported physical activity (p(Int) = 0.004) was observed. A BMI difference of 0.53 (SE 0.42) kg/m(2) was found when comparing physically passive homozygous C-allele carriers with physically passive G-allele carriers. No interactions between the two variants and FTO rs9939609 and MC4R rs17782313 were observed.
The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms play no apparent role in the development of common forms of obesity in the Danish population. However, if replicated, the INSIG2 rs7566605 may influence the level of BMI in combination with the level of physical activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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