Brain atrophy in type 2 diabetes: regional distribution and influence on cognition.

OBJECTIVE: Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function. RESEARCH DESIGN AND METHODS: This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures. RESULTS: T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume. CONCLUSIONS: Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.

The influence of gestational stage on urinary iodine excretion in pregnancy.

INTRODUCTION: Median urinary iodine concentration (UIC) is the most commonly used indicator of population iodine nutrition. However, its validity as an indicator of dietary intake relies on a stable relationship between dietary iodine intake and urinary excretion. Physiological alterations in normal pregnancy, such as increased glomerular filtration rate, potentially invalidate UIC as an assessment tool in pregnancy. OBJECTIVE: The objective of the study was to document the impact of advancing gestation on UIC in normal pregnancy and determine whether the current reference intervals for general population iodine monitoring are appropriate for use in the context of pregnancy. DESIGN: Tasmania has a well-described history of mild iodine deficiency (school-age median UIC of 84 microg/liter). We assessed UIC in 759 urine samples from 431 women attending the Antenatal Clinic at the Royal Hobart Hospital, Tasmania's primary teaching hospital. MAIN OUTCOME: The overall median UIC during pregnancy was 75 microg/liter (95% confidence interval 70.03-79.97 microg/liter) at a median gestation of 19.4 wk. Stratification by gestation, however, revealed a dynamic relationship between ioduria and gestation. Median UIC was elevated in early pregnancy and subsequently declined with advancing gestation. CONCLUSION: In this mildly iodine-deficient population, current reference intervals for UIC overestimated the adequacy of iodine nutrition during the first and early second trimester of pregnancy. Gestation-specific UIC reference intervals are required to classify iodine nutrition during pregnancy. This is particularly important in populations with borderline iodine deficiency.

A prospective study of urinary electrolytes and bone turnover in adolescent males.

BACKGROUND & AIMS: The role of excessive salt on bone metabolism in children is uncertain. The aim of this 6-week prospective study was to describe the association between urinary electrolytes and bone turnover markers in a convenience sample of adolescent boys (N = 136, mean age 16 yr). METHODS: Urinary electrolytes (sodium, potassium, calcium and magnesium) were assessed on spot overnight urines on three occasions to minimise regression dilution bias. Bone turnover was assessed by bone specific alkaline phosphatase (BAP) and urinary pyridinoline (PYR) at baseline and follow up. RESULTS: In multivariate analysis, urinary sodium (but not other electrolytes) was positively associated with both PYR and BAP both before and after taking short-term growth into account (both p < 0.05) and explained 3-6% of the variation in bone turnover markers. Urinary sodium was associated with urinary magnesium (r = +0.26, p < 0.05) but only weakly with calcium (r = +0.18, p = 0.08). Urinary potassium was significantly associated with urinary magnesium (r = -0.24, p < 0.05). CONCLUSION: High urinary sodium (which largely reflects dietary sodium intake in our location) results in a high bone turnover state in adolescent boys which is most likely detrimental for bone. Other urinary electrolytes are not related to bone turnover but may influence bone via other pathways.

Vitamin D insufficiency in adolescent males in Southern Tasmania: prevalence, determinants, and relationship to bone turnover markers.

There are limited data on vitamin D insufficiency in healthy children. The aim of this study was to describe the prevalence and determinants of vitamin D insufficiency and its association with bone turnover in adolescent boys (N = 136, mean age 16 years). Sun exposure and physical activity were assessed by questionnaire. Vitamin D stores were assessed by serum 25-hydroxyvitamin D3 (25[OH]D3). Bone turnover was assessed by bone-specific alkaline phosphatase (BAP) and urinary pyridinoline (PYR) to creatinine (Cr) ratio (mmol PYR/micromol Cr). The mean 25(OH)D3 level was low (44 nmol/l; 68% < 50 nmol/l; range, 16-87) and was associated with self-reported sun exposure on winter weekends (r = 0.23, p = 0.01), school holidays (r = 0.22, p = 0.01), and weekdays (r = 0.17, p = 0.05). It was also associated with number of sports (r = 0.34, p < 0.001) and vigorous activity (r = 0.22, p = 0.01) but not television, computer, and video watching (r = -0.04, p = 0.68). In multivariate analysis, number of sports but not total sun exposure remained significantly associated with 25(OH)D3. Furthermore, 25(OH)D3 was significantly associated with BAP in cutpoint analysis (cutpoint 55 nmol/l, p = 0.03) but not continuous analysis (r = -0.12, p = 0.16) and PYR in both forms (r = -0.23, p = 0.01, cutpoint 43 nmol/l, p = 0.01). In conclusion, vitamin D insufficiency is common in healthy adolescent boys in winter in our setting, is primarily derived from sports-related sun exposure, and is associated with bone turnover markers. These data suggest that a 25(OH)D3 level of at least 43-55 nmol/l is required for optimal bone health in children.