Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on ...between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10
), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7.5% per allele, P = 4.9 × 10
and 7.3% per allele, P = 7.5 × 10
, respectively). Variants that increase mean and between-subject variance in fasting glucose levels tend to increase T2D risk, whereas those that increase the mean but reduce variance do not (r
= 0.61). The variants that increase between-subject variance increase fasting glucose heritability estimates. Intuitively, our results show that increasing the mean and variance of glucose levels is more likely to cause pathologically high glucose levels than increase in the mean offset by a decrease in variance.
Title. Instruments to tailor care of people with type 2 diabetes.
Aim. This paper is a report of a study conducted to assess the effectiveness of an educational intervention for people with type 2 ...diabetes based on self‐completed instruments to identify particular areas of self‐care needs.
Background. Diabetes is a demanding disease which requires self‐care. Instruments that identify self‐care needs or factors affecting self‐care can be helpful to detect level of self‐care, distress or knowledge among individuals with diabetes.
Methods. Participants were randomized into intervention (n = 28) or control groups (n = 25). Both groups answered five validated instruments three times, at baseline and after 3 and 6 months, and biological measurements were conducted simultaneously. The intervention was based on an empowerment approach. The study started in November 2005 and lasted until March 2007.
Findings. There was no statistically significant difference between groups in level of glycated haemoglobin postintervention as it reduced statistically significantly in both groups between baseline and 3 months but increased again after 6 months. There was no statistically significant difference between groups in body mass index reduction; the intervention group achieved a statistically significant body mass index reduction but this was unchanged in the control group. No statistically significant differences between groups were found in scores for empowerment, well‐being and distress. There was a statistically significant difference between groups in knowledge postintervention.
Conclusion. Use of instruments to identify self‐care needs can enable patient‐tailored care as it allows direct focusing on issues that are challenging and of relevance for each individual. It seems to be feasible to use the telephone to conduct an empowering educational intervention after one meeting.
Nerve conduction (NC) studies generate measures of peripheral nerve function that can reveal underlying pathology due to axonal loss, demyelination or both. We perform a genome-wide association study ...of sural NC amplitude and velocity in 7045 Icelanders and find a low-frequency splice-donor variant in PRPH (c.996+1G>A; MAF = 1.32%) associating with decreased NC amplitude but not velocity. PRPH encodes peripherin, an intermediate filament (IF) protein involved in cytoskeletal development and maintenance of neurons. Through RNA and protein studies, we show that the variant leads to loss-of-function (LoF), as when over-expressed in a cell line devoid of other IFs, it does not allow formation of the normal filamentous structure of peripherin, yielding instead punctate protein inclusions. Recall of carriers for neurological assessment confirms that from an early age, homozygotes have significantly lower sural NC amplitude than non-carriers and are at risk of a mild, early-onset, sensory-negative, axonal polyneuropathy.
Objective: To investigate relationships between body mass index (BMI) and mortality in diabetes where obesity has been paradoxically associated with lower mortality risk than normal weight and to ...examine the possible role of muscle, adiposity and function.
Design: Participants aged 66‐96 years with diabetes from self‐report, medication or fasting glucose 蠅7mmol/l in the AGES‐Reykjavik Study. BMI was classified as normal weight (18.5‐24.9kg/m2, N=114) or overweight/obese (蠅25.0kg/m2, N=520). Thigh muscle area, abdominal and thigh adipose depots were assessed with computed tomography. Function was assessed from gait speed and leg strength.
Outcome: Mortality risk (hazard ratios (HR) and 95% confidence intervals (CI)) over a mean of 6.5 years were assessed by Cox models, reference category overweight/obese.
Results: In adjusted models (demographics, diabetes duration, medications, blood pressure, lipids, waist circumference, mid‐life BMI, smoking, microalbuminuria, inflammation and hypertension), normal weight participants had higher mortality risk (HR 1.69 95% CI 1.10‐2.61) than overweight/obese participants. Risk remained with adjustment for adipose depots and strength but was attenuated with adjustment for muscle area (HR 1.33 95% CI 0.86‐2.06) and gait speed (HR 1.54, 95% CI 0.97‐2.43).
Conclusion: Muscle size and function may help explain the obesity paradox among adults with diabetes.
Grant Funding Source: Supported by NIH contract N01‐AG012100, the NIA Intramural Research Program, Hjartavernd (the Icelan
ObjectiveTo examine if the beneficial effect of statin medication on mortality seen in randomised clinical trials of type 2 diabetes applies equally to observational studies in the general population ...of older people.DesignA prospective, population-based cohort study.SettingReykjavik, Iceland.Participants5152 men and women from the Age, Gene/Environment Susceptibility-Reykjavik Study, mean age 77 years, range of 66–96 years.Main outcome measureCardiovascular and all-cause mortalities and the RR of dying according to statin use and history of coronary heart disease (CHD) in persons with type 2 diabetes and those without diabetes with a median follow-up time of 5.3 years, until end of 2009.ResultsThe prevalence of type 2 diabetes was 12.4% of which 35% used statins. Statin use was associated with a 50% (95% CI 8% to 72%) lower cardiovascular mortality and 53% (29% to 68%) lower all-cause mortalities in persons with diabetes. For those without diabetes, statin use was associated with a 16% (−24% to 43%) lower cardiovascular and 30% (11% to 46%) lower all-cause mortalities. Persons with diabetes using statins had a comparable risk of cardiovascular and all-cause mortality to that of the general population without diabetes. The effect was independent of the level of glycaemic control.ConclusionThis observational study lends important support to existing data from randomised clinical trials. These data suggest that in the general population of older people with diabetes, statin medication markedly reduces the excess cardiovascular and all-cause mortality risk, irrespective of the presence or absence of coronary heart disease or glucose-lowering medication.
A decline in mortality rates due to cardiovascular diseases and all-cause mortality has led to increased life expectancy in the Western world in recent decades. At the same time, the prevalence of ...type 2 diabetes, a disease associated with a twofold excess risk of cardiovascular disease and mortality, has been increasing. The objective of this study was to estimate the secular trend of cardiovascular and all-cause mortality rates in two population-based cohorts of older persons, with and without type 2 diabetes, examined 11 years apart.
1506 participants (42% men) from the population-based Reykjavik Study, examined during 1991-1996 (median 1993), mean age 75.0 years, and 4814 participants (43% men) from the AGES-Reykjavik Study, examined during 2002-2006 (median 2004), mean age 77.2 years, age range in both cohorts 70-87 years. The main outcome measures were age-specific mortality rates due to cardiovascular disease and all causes, over two consecutive 5.7- and 5.3-year follow-up periods.
A 32% decline in cardiovascular mortality rate and a 19% decline in all-cause mortality rate were observed between 1993 and 2004. The decline was greater in those with type 2 diabetes, as illustrated by the decline in the adjusted hazard ratio of cardiovascular mortality in individuals with diabetes compared to those without diabetes, from 1.88 (95% CI 1.24-2.85) in 1993 to 1.46 (95% CI 1.11-1.91) in 2004. We also observed a concurrent decrease in major cardiovascular risk factors in both those with and without diabetes. A higher proportion of persons with diabetes received glucose-lowering, hypertensive and lipid-lowering medication in 2004.
A decline in cardiovascular and all-cause mortality rates was observed in older persons during the period 1993-2004, in both those with and without type 2 diabetes. This decline may be partly explained by improvements in cardiovascular risk factors and medical treatment over the period studied. However, type 2 diabetes still persists as an independent risk factor for cardiovascular mortality.
OBJECTIVE Placental 11β‐hydroxysteroid dehydrogenase (11β‐HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth ...retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11β‐HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas.
DESIGN Placentas were obtained from randomly selected normal term deliveries. The maternal circuit was perfused with physiological concentration of cortisol, the fetal effluent collected and steroid metabolites separated and quantified using silica columns (Sep‐pak Plus) and HPLC.
RESULTS Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. Cortisone was the only product of cortisol metabolism. Inhibition of 11β‐HSD with glycyrrhetinic acid allowed cortisol to gain direct access to the fetal circulation.
CONCLUSION We conclude that human placental 11β‐HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.
Epidemiologic studies suggest a link between fetal and childhood growth and later coronary artery disease (CAD). The influence of adult body size on the relation between birth size and CAD has not ...been thoroughly studied.
We investigated the association between birth and adult sizes and CAD within a population with higher birth weight and a lower incidence of and mortality rate from CAD than those seen in other Scandinavian populations.
Fatal or nonfatal CAD was ascertained in 2399 men and 2376 women born in the Greater Reykjavik area between 1914 and 1935. Birth size was obtained from the National Archives. Anthropometric measurements in adults were obtained from the randomized prospective Reykjavik Study.
CAD was inversely related to birth length (P for trend = 0.029) in men but was not significantly related to birth weight or ponderal index (kg/m(3)). In men who were born short (< or = 50.5 cm) and who became tall adults (either 175-180.5 or > 180.5 cm), the odds ratios (95% CI) for CAD were 1.9 (1.1, 3.1) and 2.2 (1.2, 4.0), respectively, when compared with men in the reference group (those born 52.5-54.0 cm long). A U-shaped relation between birth size and CAD was found for women.
Size at birth has an effect on CAD, but the effect is modified by adult body size. This confirms that environmental factors operate in both the prenatal and postnatal periods with regard to the development of CAD. The large birth size seen among Icelanders may explain the lower incidence and mortality rate of CAD in Iceland than are seen in other white populations.
We evaluated midlife risk factors of developing type 2 diabetes mellitus (T2DM) in late life in a population-based study of older persons. A cohort of 2,251 persons, aged 65-96, participated in ...AGES-Reykjavik in 2002-2004; all attended the Reykjavik Study 26 years earlier, at the mean age of 50. Based on glucometabolic status in 2002-2004 the participants are divided into a normoglycemic control group (n = 1,695), an impaired fasting glucose (IFG) group (n = 313) and T2DM group (n = 243). Change in risk parameters from midlife is evaluated retrospectively in these three groups. Since examined earlier 14.3% of men and 8.2% of women developed T2DM. A family history of diabetes was reported in 39.5% of T2DM compared to 19.3% in both IFG and normoglycemics. The T2DM and IFG groups currently have higher levels of fasting triglycerides, greater body mass index (BMI) and higher systolic blood pressure than normoglycemics and this difference was already apparent in midlife. In late life, two or more metabolic syndrome criteria are present in 60% of the T2DM groups compared to 25% in normoglycemic groups. T2DM with impaired cardiovascular health is more marked in women than men when compared with normoglycemics. Family history and higher levels of BMI, triglycerides and systolic blood pressure in midlife are associated with the development of T2DM in late life, suggesting risk can be evaluated long before onset. A continued rise in risk factors throughout life allows for more aggressive measures in preventing or delaying development of T2DM and its effect on cardiovascular health.
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