Context: Few prospective intervention studies have examined the effect of continuous positive airway pressure (CPAP) therapy on cardiovascular disease (CVD) risk factors in diabetes. Objective: Our objective was to determine whether CPAP improves CVD risk factors in patients with type 2 diabetes and obstructive sleep apnea (OSA). Design and Setting: This was a randomized parallel group intervention trial in an urban Australian community. Patients: Fifty-nine participants of the Fremantle Diabetes Study Phase II at high risk for OSA consented to confirmatory polysomnography followed by randomization to a 3-month CPAP intervention initiated early (<1 wk) or late (1–2 months). Main Outcome Measures: Patients were assessed before and 1 and 3 months after CPAP started. Tests for repeated measures were used to compare variables of interest over time. Results: Forty-four patients (75%) completed the study. Their mean ± sd age was 66.1 ± 8.8 yr, and 61.4% were male. Completers and noncompleters had similar age, sex, diabetes duration, apnea-hypopnea index, and Epworth Sleepiness Scale (P ≥ 0.29). There were no differences in outcome between early and late randomization, and the data were pooled. The Epworth Sleepiness Scale decreased between entry and 1 month [−4.8 (−6.5 to −3.1), P < 0.001]. Blood pressure improved between entry and 3 months (from 149 ± 23/80 ± 12 to 140 ± 18/73 ± 13 mm Hg; P ≤ 0.007). Pulse rate declined within the first month [−6 (−10 to −2) beats/min, P = 0.002]. Glycemic control and serum lipids, which were mostly within recommended target ranges at entry, did not change. Conclusions: Three months of CPAP in community-based people with type 2 diabetes significantly decreased blood pressure and pulse rate but did not influence metabolic control.

Aims: fear of falling is an important falls-related symptom that has received little attention in studies of falls risk in older adults with type 2 diabetes. Methods: matched pairs of participants with diabetes or with normoglycaemia (n = 186 per group) recruited from a community-based survey underwent an assessment of fear of falling and associated falls risk factors. Multivariate methods examined associations between fear of falling and risk factors for history of recent falls. Results: compared with the normoglycaemic participants, those with diabetes had worse mobility (slow timed Up and Go test times: 16.2 versus 4.9%, P < 0.01), more fear of falling (24.2 versus 15.1%, P < 0.05) and more activity restriction from fear of falling (indoors: 14.0 versus 4.8%, P = 0.006), but there was no increase in reported recent falls. In the combined sample, a history of recent falls was negatively associated with fear-related limitation of outdoor activities (odds ratio (95% confidence interval): 0.30 (0.15–0.58), P < 0.001) and positively associated with age (1.65 (1.20–2.28) per 10-year increase, P = 0.002) and use of antidepressants (2.14 (1.02–4.50, P = 0.044). The frequency of falls in those with recurrent falls was negatively associated with measures of balance. Conclusions: type 2 diabetes is associated with increased fear of falling and fear-associated activity restriction, and this modifies the risk of falls even in the face of increased falls risk factors including worse mobility. Future studies of falls in diabetes need to consider that fear of falling is an important modifier of the relationship between risk factors and falls.

Background: Low levels of serum adiponectin have been linked to central obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. Variants inADIPOQ, the gene encoding adiponectin, have been shown to influence serum adiponectin concentration, and along with variants in the adiponectin receptors (ADIPOR1andADIPOR2) have been implicated in metabolic syndrome and type 2 diabetes. This study aimed to comprehensively investigate the association of common variants inADIPOQ, ADIPOR1andADIPOR2with serum adiponectin and insulin resistance syndromes in a large cohort of European-Australian individuals.Methods: Sixty-four tagging single nucleotide polymorphisms inADIPOQ,ADIPOR1andADIPOR2were genotyped in two general population cohorts consisting of 2,355 subjects, and one cohort of 967 subjects with type 2 diabetes. The association of tagSNPs with outcomes were evaluated using linear or logistic modelling. Meta-analysis of the three cohorts was performed by random-effects modelling.Results: Meta-analysis revealed nine genotyped tagSNPs inADIPOQsignificantly associated with serum adiponectin across all cohorts after adjustment for age, gender and BMI, including rs10937273, rs12637534, rs1648707, rs16861209, rs822395, rs17366568, rs3774261, rs6444175 and rs17373414. The results of haplotype-based analyses were also consistent. Overall, the variants in theADIPOQgene explained <5% of the variance in serum adiponectin concentration. None of theADIPOR1/R2tagSNPs were associated with serum adiponectin. There was no association between any of the genetic variants and insulin resistance or metabolic syndrome. A multi-SNP genotypic risk score forADIPOQalleles revealed an association with 3 independent SNPs, rs12637534, rs16861209, rs17366568 and type 2 diabetes after adjusting for adiponectin levels (OR=0.86, 95% CI=(0.75, 0.99), P=0.0134).Conclusions: Genetic variation inADIPOQ, but not its receptors, was associated with altered serum adiponectin. However, genetic variation inADIPOQand its receptors does not appear to contribute to the risk of insulin resistance or metabolic syndrome but did for type 2 diabetes in a European-Australian population.

Low serum magnesium concentrations have been associated with cardiovascular disease risk and outcomes in some general population studies but there are no equivalent studies in diabetes. Metformin may have cardiovascular benefits beyond blood glucose lowering in type 2 diabetes but its association with hypomagnesemia appears paradoxical. The aim of this study was to examine relationships between metformin therapy, magnesium homoeostasis and cardiovascular disease in well-characterized type 2 patients from the community. We studied 940 non-insulin-treated patients (mean±SD age 63.4±11.6 years, 49.0% males) from the longitudinal observational Fremantle Diabetes Study Phase I (FDS1) who were followed for 12.3±5.3 years. Baseline serum magnesium was measured using stored sera. Multivariate methods were used to determine associates of prevalent and incident coronary heart disease (CHD) and cerebrovascular disease (CVD) as ascertained from self-report and linked morbidity/mortality databases. 19% of patients were hypomagnesemic (serum magnesium <0.70 mmol/L). Patients on metformin, alone or combined with a sulfonylurea, had lower serum magnesium concentrations than those on diet alone (P<0.05). There were no independent associations between serum magnesium or metformin therapy and either CHD or CVD at baseline. Incident CVD, but not CHD, was independently and inversely associated with serum magnesium (hazard ratio (95% CI) 0.28 (0.11–0.74); P = 0.010), but metformin therapy was not a significant variable in these models. Since hypomagnesemia appears to be an independent risk factor for CVD complicating type 2 diabetes, the value of replacement therapy should be investigated further, especially in patients at high CVD risk.

Neurocognitive dysfunction is a core feature of schizophrenia with particularly prominent deficits in verbal episodic memory. The molecular basis of this memory impairment is poorly understood and its relatedness to normal variation in memory performance is unclear. In this study, we explore, in a sample of cognitively impaired schizophrenia patients, the role of polymorphisms in seven genes recently reported to modulate episodic memory in normal subjects. Three polymorphisms (GRIN2B rs220599, GRM3 rs2189814 and PRKCA rs8074995) were associated with episodic verbal memory in both control and patients with cognitive deficit, but not in cognitively spared patients or the pooled schizophrenia sample. GRM3 and PRKCA acted in opposite directions in patients compared to controls, possibly reflecting an abnormal brain milieu and/or adverse environmental effects in schizophrenia. The encoded proteins balance glutamate signalling vs. excitotoxicity in complex interactions involving the excitatory amino acid transporter 2 (EAAT2), implicated in the dysfunctional glutamatergic signalling in schizophrenia. Double carrier status of the GRM3 and PRKCA minor alleles was associated with lower memory test scores and with increased risk of schizophrenia. Single nucleotide polymorphism (SNP) rs8074995 lies within the PRKCA region spanned by a rare haplotype associated with schizophrenia in a recent UK study and provides further evidence of PRKCA contribution to memory impairment and susceptibility to schizophrenia. Our study supports the utility of parsing the broad phenotype of schizophrenia into component cognitive endophenotypes that reduce heterogeneity and enable the capture of potentially important genetic associations.