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Biomedical subjects

Karl-Fredrik Eriksson

Publications and source records attributed to Karl-Fredrik Eriksson.

6 recordsLinked to original sources
PubMed2005

Complement C3 is a risk factor for the development of diabetes: a population-based cohort study.

Cross-sectional studies have reported strong correlations between plasma levels of complement C3, insulin, and glucose. This prospective study explored whether elevated levels of C3, C4, and other inflammation-sensitive plasma proteins (ISPs; fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with the development of diabetes. Plasma proteins were measured in 2,815 nondiabetic healthy men, age 38-50 years, who were reexamined after a mean follow-up of 6.1 years. Diabetes development (n = 123) was studied in relation to baseline levels of plasma proteins. After adjusting for age, screening year, and glucose at baseline, the odds ratio (95% CI) for developing diabetes was 1.00, 2.4 (1.1-5.3), 2.9 (1.4-6.0), and 5.6 (2.8-10.9), respectively, for men with C3 in the 1st, 2nd, 3rd, and 4th quartiles (trend: P < 0.00001). Fibrinogen, haptoglobin, C4, and the number of elevated ISPs were also related to future diabetes in this model. Only C3 was significantly associated with diabetes development after further adjustments for potential confounders, including BMI, insulin, and other inflammatory markers. We concluded that the risk of developing diabetes is related to levels of complement C3.

Blood Glucose↗
PubMed2005

Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men.

OBJECTIVE: The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity and mitochondrial function in men. RESEARCH DESIGN AND METHODS: A total of 60 men (mean age 60.5 +/- 1.2 years) had a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by measuring maximal aerobic capacity (V(O2max)) and expression of oxidative phosphorylation genes in skeletal muscle. RESULTS: A total of 45% of subjects had normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2 diabetes. Testosterone levels were positively correlated with insulin sensitivity (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had a BMI >25 kg/m(2) and a threefold higher prevalence of the metabolic syndrome than their eugonadal counterparts (n = 50); this relationship held true after adjusting for age and sex hormone-binding globulin but not BMI. Testosterone levels also correlated with V(O2max) (r = 0.43, P < 0.05) and oxidative phosphorylation gene expression (r = 0.57, P < 0.0001). CONCLUSIONS: These data indicate that low serum testosterone levels are associated with an adverse metabolic profile and suggest a novel unifying mechanism for the previously independent observations that low testosterone levels and impaired mitochondrial function promote insulin resistance in men.

Adult↗
PubMed2003

PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.

DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.

Animals↗
PubMed2003

Inflammation-sensitive plasma proteins, diabetes, and mortality and incidence of myocardial infarction and stroke: a population-based study.

This study explores the relationship of inflammation-sensitive plasma proteins (ISPs) with the prevalence of diabetes and the interrelationships between ISPs and diabetes in the prediction of death and incidence of myocardial infarction and stroke. Plasma levels of fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were assessed in 6,050 men, aged 28-61 years. All-cause and cardiovascular mortality and incidence of myocardial infarction and stroke were monitored over 18.7 +/- 3.7 years. Prevalence of diabetes (n = 321) was significantly associated with ISP levels among overweight and obese men but not among men with BMI <25 kg/m(2). The association was similar for insulin resistance according to homeostasis model assessment. High ISP levels (two or more ISPs in the top quartile) increased the cardiovascular risk among diabetic men. The risk factor-adjusted relative risks for cardiovascular mortality, myocardial infarction, and stroke were 2.8 (CI 1.8-4.5), 2.2 (1.5-3.2), and 2.5 (1.4-4.6), respectively, for diabetic men with high ISP levels (reference: nondiabetic men with low ISP levels). The corresponding risks for diabetic men with low ISP levels were 1.8 (1.1-3.0), 1.3 (0.8-2.1), and 1.2 (0.6-2.5), respectively. In conclusion, in this population-based cohort, diabetes was associated with increased ISP levels among overweight and obese men but not among men with normal weight. High ISP levels increased the cardiovascular risk similarly in diabetic as compared with nondiabetic men.

Blood Pressure↗
PubMed2002

Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance.

Oxidative stress has been ascribed a role in the pathogenesis of diabetes and its complications, and stress proteins have been shown to protect organisms in vitro and in vivo against oxidative stress. To study the putative role of one of the most abundant cytoprotective stress proteins, inducible cytoplasmic 72-kDa-mass heat shock protein (Hsp-72), in the pathogenesis of diabetes, we measured its mRNA concentration in muscle biopsies from six type 2 diabetic patients and six healthy control subjects (protocol 1) as well as in 12 twin pairs discordant for type 2 diabetes and 12 control subjects undergoing a euglycemic-hyperinsulinemic clamp in combination with indirect calorimetry (protocol 2). The amount of Hsp-72 mRNA in muscle was significantly lower in type 2 diabetic patients than in healthy control subjects (in protocol 1: 5.2 +/- 2.2 vs. 53 +/- 32 million copies of Hsp-72 mRNA/microg total RNA, n = 6, P = 0.0039; in protocol 2: 3.2 +/- 3.3 vs. 43 +/- 31 million copies of Hsp-72 mRNA/microg total RNA, n = 12, P = 0.0001). Hsp-72 mRNA levels were also markedly reduced in the nondiabetic co-twins compared with healthy control subjects (5.8 +/- 5.0 vs. 43 +/- 31, n = 12, P = 0.0001), but they were also statistically significantly different from their diabetic co-twins when the difference between the pairs was compared (P = 0.0280). Heat shock protein mRNA content in muscle of examined patients correlated with the rate of glucose uptake and other measures of insulin-stimulated carbohydrate and lipid metabolism. In conclusion, the finding of decreased levels of Hsp-72 mRNA in skeletal muscle of patients with type 2 diabetes and its relationship with insulin resistance raises the question of whether heat shock proteins are involved in the pathogenesis of skeletal muscle insulin resistance in type 2 diabetes.

Blood Glucose↗