Health Literacy predicts incident foot ulcers after 4 years - the SHELLED cohort study.

AIMS/HYPOTHESIS: To determine whether health literacy is associated with an index diabetes-related foot ulcer (DFU). METHODS: The SHELLED Study is a 4-year prospective study of people with diabetes aged over 40 with no history of DFU. The primary outcome was development of a first foot ulcer. Health Literacy was measured using the short form Test of Functional Health Literacy in Adults (s-TOFHLA) and nine domains of the Health Literacy Questionnaire (HLQ). RESULTS: Of 222 participants, 191 (86.0%) completed the study, of whom 13 (5.9%) developed an incident ulcer. In multivariable models, every unit increase in S-TOFHLA was associated with a reduced odds of foot ulcer development by 6% (OR 0.94, 95% CI 0.88 to 0.99). Better scores on two HLQ domains reduced the odds of foot ulcer (actively managing my health (OR 0.23, 95% CI 0.08 to 0.65) and understanding health information well enough to know what to do (OR 0.39, 95% CI 0.19 to 0.78). This was independent of baseline risk for foot disease. CONCLUSIONS/INTERPRETATION: These data provide novel evidence that health literacy is an important clinical risk factor for index foot ulceration. This is an area of potential focus for research and development of educational programs or policy aimed at reducing development of incident foot ulceration.

Impaired postprandial adipose tissue microvascular blood flow responses to a mixed-nutrient meal in first-degree relatives of adults with type 2 diabetes.

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH-, n = 13), with at least one parent with T2D (FH+, n = 14) and clinically diagnosed T2D (n = 11) underwent a mixed meal challenge (MMC). Metabolic responses [blood glucose, plasma insulin, plasma nonesterified fatty acids (NEFAs), and fat oxidation] were measured before and during the MMC. MBF in truncal subcutaneous adipose tissue was assessed by contrast ultrasound while fasting and 60 min post-MMC. FH+ had normal blood glucoses, increased adiposity, and impaired post-MMC adipose tissue MBF (Δ0.70 ± 0.22 vs. 2.45 ± 0.60 acoustic intensity/s, P = 0.007) and post-MMC adipose tissue insulin resistance (Adipo-IR index; Δ45.5 ± 13.9 vs. 7.8 ± 5.1 mmol/L × pmol/L, P = 0.007) compared with FH-. FH+ and T2D had an impaired ability to suppress fat oxidation post-MMC. Fat oxidation incremental area under the curve (iAUC) (35-55 min post-MMC, iAUC) was higher in FH+ and T2D than in FH- (P = 0.005 and 0.009, respectively). Postprandial MBF was negatively associated with postprandial fat oxidation iAUC (P = 0.01). We conclude that apparently healthy FH+ individuals display blunted postprandial adipose tissue MBF that occurs in parallel with adipose tissue insulin resistance and impaired suppression of fat oxidation, which may help explain their heightened risk for developing T2D.NEW & NOTEWORTHY Adipose tissue blood flow plays a key role in postprandial nutrient storage. People at-risk of type 2 diabetes have impaired postmeal adipose tissue blood flow. Impaired adipose tissue blood flow is associated with altered fat oxidation. Risk of type 2 diabetes may be elevated by poor adipose tissue blood flow.

Cognition, educational attainment and diabetes distress predict poor health literacy in diabetes: A cross-sectional analysis of the SHELLED study.

OBJECTIVES: To identify factors that predict poor health literacy amongst people with diabetes. DESIGN: Cross-sectional analysis of baseline data from a prospective study of diabetic foot disease. SETTING: Patients attending a tertiary hospital diabetes outpatient clinic in Tasmania, Australia. PARTICIPANTS: 222 people with diabetes mellitus, aged >40 years, with no history of foot ulceration, psychotic disorders or dementia. OUTCOME MEASURES: Health literacy was measured using the short form Test of Functional Health Literacy in Adults (functional health literacy), and the Health Literacy Questionnaire (HLQ), which measures nine domains of health literacy. Predictors included demographic characteristics, cognition, diabetes distress, depression, and educational attainment. RESULTS: In multivariable analysis, greater educational attainment (OR 0.88, 95% CI 0.76, 0.99) and poorer cognition (OR 0.71, 95% CI 0.63, 0.79) were associated with poorer functional health literacy. Age was negatively associated with domains of appraisal of health information and ability to find good health information (both beta = -0.01). Educational attainment was positively associated with four domains, namely having sufficient information to manage my health, actively managing my health, appraisal of and ability to find good health information (beta ranging from +0.03 to 0.04). Diabetes distress was negatively associated with five domains: having sufficient information to manage my health, social support for health, ability to actively engage with healthcare providers, navigating the healthcare system and ability to find good health information (beta ranging from -0.14 to -0.18). CONCLUSION: Poorer cognition and poorer educational attainment may be detrimental for an individual's functional health literacy, and education, diabetes distress and older age detrimental across multiple health literacy domains. Clinicians and policy makers should be attuned to these factors when communicating with people with diabetes and in designing healthcare systems to be more health-literacy friendly in order to improve diabetes outcomes.

Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes.

AIMS/HYPOTHESIS: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in individuals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal. METHODS: In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+; i.e. a parent with type 2 diabetes; n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC. RESULTS: Despite normal blood glucose concentrations, FH+ individuals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH-; p < 0.05) during the MMC. The MMC increased forearm muscle microvascular blood volume in both the FH- (1.3-fold, p < 0.01) and FH+ (1.3-fold, p < 0.05) groups but not in participants with type 2 diabetes. However, the MMC increased MBF (1.9-fold, p < 0.01), brachial artery diameter (1.1-fold, p < 0.01) and brachial artery blood flow (1.7-fold, p < 0.001) and reduced vascular resistance (0.7-fold, p < 0.001) only in FH- participants, with these changes being absent in FH+ and type 2 diabetes. Participants with type 2 diabetes displayed significantly higher vascular stiffness (p < 0.001) compared with those in the FH- and FH+ groups; however, vascular stiffness did not change during the MMC in any participant group. CONCLUSIONS/INTERPRETATION: Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC.

Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = -0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.

Oral glucose challenge impairs skeletal muscle microvascular blood flow in healthy people.

Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P < 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P < 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.

Impairments in Adipose Tissue Microcirculation in Type 2 Diabetes Mellitus Assessed by Real-Time Contrast-Enhanced Ultrasound.

BACKGROUND: In obesity and type 2 diabetes mellitus (T2D), adipose tissue expansion (because of larger adipocytes) results in reduced microvascular density which is thought to lead to adipocyte hypoxia, inflammation, and reduced nutrient delivery to the adipocyte. Adipose tissue microvascular responses in humans with T2D have not been extensively characterized. Furthermore, it has not been determined whether impaired microvascular responses in human adipose tissue are most closely associated with adiposity, inflammation, or altered metabolism. METHODS AND RESULTS: Overnight-fasted healthy controls (n=24, 9 females/15 males) and people with T2D (n=21, 8 females/13 males) underwent a body composition scan (dual-energy X-ray absorptiometry), an oral glucose challenge (50 g glucose) and blood analysis of clinical chemistries and inflammatory markers. Abdominal subcutaneous adipose tissue microvascular responses were measured by contrast-enhanced ultrasound at baseline and 1-hour post-oral glucose challenge. Adipose tissue microvascular blood volume was significantly elevated in healthy subjects 1-hour post-oral glucose challenge; however, this effect was absent in T2D. Adipose tissue microvascular blood flow was lower in people with T2D at baseline and was significantly blunted post-oral glucose challenge compared with controls. Adipose tissue microvascular blood flow was negatively associated with truncal fat (%), glucoregulatory function, fasting triglyceride and nonesterified fatty acid levels, and positively associated with insulin sensitivity. Truncal fat (%), systolic blood pressure, and insulin sensitivity were the only correlates with microvascular blood volume. Systemic inflammation was not associated with adipose tissue microvascular responses. CONCLUSIONS: Impaired microvascular function in adipose tissue during T2D is not conditionally linked to systemic inflammation but is associated with other characteristics of the metabolic syndrome (obesity, insulin resistance, hyperglycemia, and dyslipidemia).

Skeletal Muscle Microvascular-Linked Improvements in Glycemic Control From Resistance Training in Individuals With Type 2 Diabetes.

OBJECTIVE: Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin's microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS: Seventeen (11 male and 6 female; 52 ± 2 years old) sedentary patients with type 2 diabetes underwent 6 weeks of whole-body RT. Before and after RT, participants who fasted overnight had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced glycation end products) and underwent an oral glucose challenge (OGC) (50 g × 2 h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed body composition. RESULTS: After RT, muscle MBF response to the OGC increased, while skin microvascular responses were unchanged. These microvascular adaptations were accompanied by improved glycemic control (fasting blood glucose, HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body mass and reductions in fasting plasma triglyceride, total cholesterol, advanced glycation end products, and total body fat. Changes in muscle MBF response after RT significantly correlated with reductions in fasting blood glucose, HbA1c, and OGC AUC with adjustment for age, sex, % body fat, and % lean mass. CONCLUSIONS: RT improves OGC-stimulated muscle MBF and glycemic control concomitantly, suggesting that MBF plays a role in improved glycemic control from RT.

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.

The effect of a fracture protocol on hospital prescriptions after minimal trauma fractured neck of the femur: a retrospective audit.

Effective therapies for the treatment of osteoporosis and fracture have been available for a number of years. Despite this, there are numerous reports indicating very low uptake rates in those admitted to hospital with fracture. The aim of this retrospective audit was to assess the impact of a fracture protocol on inpatient prescriptions of osteoporosis therapy. A fracture protocol was arrived at by consensus and was based on recommendations from the Australian Fracture Prevention Summit, which included specific advice on the commencement in hospital of calcium, vitamin D, synthetic estrogen receptor modulators (SERMs) and bisphosphonates. We studied subjects who were treated for fractured neck of the femur at Royal Hobart Hospital from March 2002 to March 2004 and included 161 prior to the start of the protocol and 93 after. As compared to the baseline period, subjects after the introduction of the protocol had higher rates of in-hospital prescription for any treatment (58 vs. 36%, P <0.01), calcium (51 vs. 26%, P <0.01), vitamin D (48 vs. 29%, P <0.01) and oral bisphosphonates (24 vs. 5%, P <0.01), but not SERMs as expected (1 vs. 1%, P =0.70). Additional factors affecting the decision to start any treatment included in-hospital death (OR 0.16, 95% CI 0.05-0.49), dementia (OR 0.39, 95% CI 0.21-0.74), a trend for female sex (OR 1.79, 95%CI 0.96-3.36), but not age. In conclusion, a structural approach to changing hospital policy from the top down is effective at substantially increasing the usage of effective therapy after fractured neck of the femur.

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.