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Moffat J Nyirenda

Publications and source records attributed to Moffat J Nyirenda.

5 recordsLinked to original sources
PubMed2006

A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet.

Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during the final 4 weeks, diets were either choline deficient or choline supplemented. In choline replete animals, high-fat feeding induced weight gain, elevated liver triglycerides (171%), hyperinsulinemia, and glucose intolerance. Choline deficiency did not affect body or adipose depot weights but amplified liver fat accumulation with high-fat diet (281%, P < 0.01). However, choline deficiency lowered fasting plasma insulin (from 983 +/- 175 to 433 +/- 36 pmol/l, P < 0.01) and improved glucose tolerance on a high-fat diet. In mice on 30% fat diet, choline deficiency increased liver mRNA levels of the rate-limiting enzyme in phosphatidylcholine synthesis and of enzymes involved in free fatty acid esterification, without affecting those of de novo lipogenesis or fatty acid oxidation. We conclude that liver fat accumulation per se does not cause insulin resistance during high-fat feeding and that choline deficiency may shunt potentially toxic free fatty acids toward innocuous storage triglyceride in the liver.

Animals↗
PubMed2005

Thyroid disease and increased cardiovascular risk.

The effects of thyroid dysfunction are thought to be reversible on restoration of euthyroidism, but postmortem and epidemiologic data suggest that subclinical or treated thyroid disease is associated with increased vascular risk. In order to determine the extent of this risk, and to explore whether the nature and/or treatment of thyroid disease are critical in this relationship, we used medical record linkage to match patients with treated thyroid disease of various etiologies with routinely collected national inpatient and daycase hospital discharge records and death records, and assessed the number of hospitalizations from cardiovascular or cerebrovascular disease or death in patients with thyroid disease and control patients. Patients treated for Graves' disease had more hospitalizations from cardiovascular disease than controls (relative risk, 1.42; 95% confidence interval, 1.20 to 1.67; p < 0.001). Toxic multinodular goiter was also associated with significantly higher rates of cardiovascular disease (relative risk, 1.50; 95% confidence interval, 1.11 to 2.02; p = 0.008). Patients with Hashimoto's thyroiditis aged over 50 years had a threefold increase in cardiovascular admissions compared to controls (23.5% and 6.5%, respectively; 95% confidence interval for difference, 6.0% to 27.9%; p = 0.003). Thus, different forms of thyroid disease were associated with increased long-term vascular risk despite restoration of euthyroidism. The mechanisms that mediate this risk are unclear but may not involve thyroid hormone abnormality.

Adult↗
PubMed2004

Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening.

AIM: To ascertain the predictive values of thyroid autoantibodies and thyrotropin (TSH) levels for subsequent thyroid dysfunction in patients with diabetes. METHODS: Review of records of 467 patients who had attended diabetes clinics for a mean of 6.1 years. Baseline autoantibody and TSH results and thyroid status at annual review were determined. RESULTS: Thyroid disorders were known in 29 patients (6.2%), and newly identified in 32 (6.9%), at presentation. Of 406 patients with normal baseline thyroid status, 24 (5.9%) developed thyroid dysfunction during 6.1 years of mean follow-up. Higher baseline TSH concentration was associated with subsequent hypothyroidism; a threshold of 1.53 mU/L, approximately defining the top quartile, provided 75% sensitivity and specificity. Both TSH greater than 1.53 mU/L and positive autoantibody status predicted thyroid dysfunction, but only TSH was significant in multivariable analysis (odds ratio, 7.74, p < 0.001). No overt thyroid dysfunction developed in 293 patients with baseline TSH levels less than 1.53 mU/l. CONCLUSIONS: Baseline TSH level may be a better predictor of thyroid dysfunction than thyroid autoantibodies in people with diabetes. Patients with TSH levels below the top quartile have a risk of thyroid dysfunction similar to the general population. It may be appropriate to stop annual thyroid screening in this group, although confirmation is required.

Adolescent↗
PubMed2003

Is programming of glucocorticoid receptor expression by prenatal dexamethasone in the rat secondary to metabolic derangement in adulthood?

OBJECTIVE: Glucocorticoids may contribute to the association between retarded growth in utero and insulin resistance in adulthood. Administration of dexamethasone (dex) to pregnant rats results in low birth weight offspring, which develop glucose intolerance, hyperinsulinaemia and hypercorticosteronaemia. This may be explained by tIssue-specific differences in expression of glucocorticoid receptors (GR) in adult offspring: GR is increased in visceral fat and liver, and decreased in hippocampus and soleus muscle. However, cause and effect between altered GR expression, hypercorticosteronaemia, and hyperinsulinaemia remains to be established. DESIGN AND METHODS: Rats were treated with dex (100 microg/kg per day) or saline during the third week of pregnancy. In 5-8-Month-old male offspring, GR expression in insulin target tIssues was quantified by RNase protection assay in rats that were adrenalectomised (ADX group), sham operated (SHAM group), or adrenalectomised with supra-physiological corticosterone replacement (CORT group) (n=7-8 per group), and in rats treated orally with vehicle, metformin (43 mg/kg per day) or rosiglitazone (1 mg/kg per day), after 3 weeks. RESULTS: Manipulation of corticosterone concentration did not affect GR mRNA in skeletal muscle or adipose. In liver, sham-operated animals showed lower GR mRNA, but there was no difference between adrenalectomised and hypercorticosteronaemic animals (SHAM 0.11+/-0.01 ratio to beta-actin, vs ADX 0.22+/-0.02, CORT 0.23+/-0.02, (values expressed as means+/-s.e.m.), P<0.001). Rosiglitazone reduced GR mRNA by approximately 30% in liver of dex- and saline-treated offspring (P<0.05), but had no effect on GR in adipose and skeletal muscle. Metformin abolished the 38% up-regulation of liver GR mRNA induced by antenatal dex and also reduced GR mRNA preferentially in muscle of dex-treated animals (0.14+/-0.01 vs 0.10+/-0.01; P=0.03). CONCLUSIONS: We conclude that neither hypercorticosteronaemia nor hyperinsulinaemia are sufficient to cause the changes in GR expression in dex-programmed rats, implying that these changes may be primary in determining the programmed insulin resistant phenotype. Normalisation of GR expression by metformin may be important in the mode of action of this anti-diabetic agent and may be especially useful to reverse-programmed up-regulation of GR.

Animals↗