Clinically significant chronic liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study

Background: Type 2 diabetes is an independent risk factor for chronic liver disease, however disease burden estimates and knowledge of prognostic indicators are lacking in community populations. Aims: To describe the prevalence and incidence of clinically significant chronic liver disease amongst community-based older people with Type 2 diabetes and to determine risk factors which might assist in discriminating patients with unknown prevalent or incident disease. Design: Prospective cohort study. Methods: Nine hundred and thirty-nine participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of non-alcoholic steatohepatitis (NASH), hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources. Results: Eight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000 person-years). Higher levels of systemic inflammation, NASH and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease (all P < 0.001). Conclusions: Our study investigations increased the known prevalence of clinically significant chronic liver disease by over 150%, confirming the suspicion of a large burden of undiagnosed disease. The disease incidence rate was lower than anticipated but still much higher than the general population rate. The ability to identify patients both with and at risk of developing clinically significant chronic liver disease allows for early intervention and clinical monitoring strategies. Ongoing work, with longer follow-up, including analysis of rates of liver function decline, will be used to define optimal risk prediction tools

Serum leptin and cognitive function in people with Type 2 diabetes

People with obesity and type 2 diabetes are at increased risk of cognitive impairment. We aimed to investigate the association of leptin with cognitive abilities in an elderly population with type 2 diabetes. We performed a cross-sectional study of 1057 men and women aged 60–75 years with type 2 diabetes living in Lothian (Scotland). A cognitive battery was administered. Prior intelligence was estimated from vocabulary testing and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning leptin levels and cognitive ability and estimated cognitive change were tested. Higher leptin levels were associated with significantly poorer estimated overall cognitive decline, and poorer performance in 2 cognitive domains assessing mental flexibility and executive function, only amongst men (p &#60; 0.05). High morning leptin levels in elderly men with type 2 diabetes are associated with estimated age-related cognitive change

Leptin levels and depressive symptoms in people with type 2 diabetes: The Edinburgh Type 2 Diabetes Study

OBJECTIVE: Depression in Type 2 diabetes is associated with obesity, cardiovascular disease, and mortality. Leptin is a plausible mediating factor because it has been related to obesity, depression, and cardiovascular disease in nondiabetic populations. We sought to assess whether leptin is related to depressive symptoms in people with Type 2 diabetes. METHODS: One thousand fifty-seven subjects (48.5% women, mean [standard deviation] age = 67.9 [4.2] years) with Type 2 diabetes were assessed for depressive symptoms using the Hospital Anxiety and Depression Scale and other clinical variables by interview and physical examination. Plasma leptin was determined by radioimmunoassay. Multiple linear regression was performed to assess the relationship between depressive symptoms and ln leptin while adjusting for other covariates. A mediation analysis was performed to test whether depressive symptoms mediated the relationship between obesity and leptin. RESULTS: In univariate analyses, symptoms of depression were related to leptin in men (r = 0.214, p &#60; .001) and women (r = 0.146, p = .007). When adjusting for other covariates including body mass index, ischemic heart disease, glycated hemoglobin, duration of diabetes, and treatment with antidepressants, insulin, or glucocorticoids, using a hierarchical multiple linear regression, depressive symptoms (ln Hospital Anxiety and Depression Scale-depression score) were significant only in men (B = 0.083, standard error = 0.037, p = .03). In the mediation analysis, depressive symptoms partially mediated the effect of obesity (body mass index) on leptin in men but not in women. CONCLUSIONS: There is a sex difference in the relationship between depressive symptoms and leptin in people with Type 2 diabetes, with a positive association in men but not in women. Adipocyte-derived factors are associated with depressive symptoms in Type 2 diabetes

Genetic associations between fibrinogen and cognitive performance in three Scottish cohorts

There is increasing evidence to suggest that elevated plasma levels of fibrinogen are associated with late-life cognitive performance. This study tested the association of single nucleotide polymorphisms in the fibrinogen alpha (FGA) and beta (FGB) genes with cognitive performance. Data were analysed from three community-dwelling populations of older persons (&gt; 50 years) in central Scotland: the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 2,091), the Edinburgh Type 2 Diabetes Study (ET2DS, n = 1,066), and the Lothian Birth Cohort 1936 (LBC1936, n = 1,091). Cognition was assessed using a battery of five, seven, and four psychometric tests, respectively. This information was used to derive a general cognitive factor. Weakly significant associations were found between the rs4220 (FGB), and rs2227412 (FGB) SNPs and a single test of cognitive performance in the AAA Trial (p &lt; 0.05). These findings did not replicate in the LBC1936 or ET2DS cohorts, except for the rs2227412 SNP, which was significantly associated with the general cognitive factor in the ET2DS (p = 3.3 x 10(-4)). A summary term that combined results from all three studies suggested that the rs2227412 genotype associated with reduced cognitive ability also associated with higher plasma fibrinogen levels. These findings suggest a tentative role for fibrinogen as a determinant of late-life cognitive performance and justify further attempts at replication in older persons