Biomedical subjects

Ian F Godsland

Publications and source records attributed to Ian F Godsland.

3 recordsLinked to original sources

PubMed2003

The minimal model: an evolving methodology.

After more than 20 years, minimal model analysis of intravenous glucose tolerance test glucose and insulin concentrations continues to be widely employed in studies of insulin sensitivity and insulin resistance. Moreover, problems encountered in solving the minimal model equations continue to find new solutions. Bayesian techniques enable prior knowledge to be incorporated into parameter estimation routines. They offer particular advantages in the measurement of insulin sensitivity with the minimal model, and provide an elegant means of improving model identification success rates and parameter precision. This comment describes the study by Agbaje and colleagues in this issue of Clinical Science that exemplifies a new phase in the evolution of minimal model practice.

Bayes Theorem↗

PubMed2003

Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes.

OBJECTIVE: Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM. PATIENTS AND MEASUREMENTS: We performed an insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose. RESULTS: Post-GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25.3 kg/m2 (23.8-27.1 kg/m2) vs. 23.1 kg/m2 (21.9-24.3 kg/m2), P = 0.03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0.6 x 10-4/min/pmol/l (0.3-1.2 x 10-4/min/pmol/l) vs. 1.5 x 10-4/min/pmol/l (1.2-1.8 x 10-4/min/pmol/l), P = 0.01] and by homeostatic model assessment [72% (49-107%) vs. 153% (113-206%), P = 0.004]; and by their higher fasting triglycerides [1.0 mmol/l (0.7-1.5 mmol/l) vs. 0.7 mmol/l (0.6-0.8 mmol/l), P = 0.001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post-GDM group (P = 0.01). Concomitant beta-cell dysfunction in the post-GDM women was revealed by their lower disposition index [0.05/min (0.02-0.10/min) vs. 0.11/min (0.09-0.14/min), P = 0.02] compared to controls. The differences in insulin sensitivity, but not those of beta-cell function, were partly, though not completely, attributable to differences in regional and total adiposity. CONCLUSIONS: European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.

Adult↗

PubMed2002

Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-alpha.

OBJECTIVES: Chronic heart failure (CHF) has emerged as an insulin-resistant state, independently of ischaemic aetiology. The underlying mechanisms of this finding are not known. Catecholamines, tumor necrosis factor alpha (TNFalpha) and leptin, the adipocyte specific hormone, have all been implicated as mediators of impaired insulin sensitivity. The purpose of this study was to examine in patients with CHF and in comparison to healthy controls subjects whether norepinephrine, TNFalpha or leptin relate to insulin sensitivity. DESIGN: 41 patients with CHF (age 60+/-2 years, NYHA I/II/III/IV 4/12/22/3, peak oxygen consumption 17.6+/-1.0 ml/kg per min) and 21 healthy controls of similar age and total and regional fat distribution were studied in a cross-sectional study. Insulin sensitivity was assessed by intravenous glucose tolerance testing using the minimal model approach; catecholamines, TNFalpha and soluble TNF receptors 1 and 2 were also measured. Total and regional body fat mass was assessed by dual energy X-ray absorptiometry. RESULTS: Insulin sensitivity was reduced in CHF patients compared to controls by 31% (P<0.01) and fasting insulin was higher in patients than in controls (79.1+/-9.7 vs. 41.4+/-6.0 pmol/l, P<0.01). Patients had, compared to healthy controls, elevated serum leptin levels (8.28+/-0.84 vs. 4.83+/-0.68 ng/ml), norepinephrine (3.45+/-0.34 vs. 1.87+/-0.16 nmol/l, both P<0.01) and soluble TNF-receptors 1 (1280+/-141 vs. 639+/-52 pg/ml) and 2 (2605+/-184 vs. 1758+/-221 pg/ml, both P<0.01). Leptin levels corrected for total body fat mass were higher in CHF patients than in controls (41.3+/-3 vs. 24.3+/-2 pg/ml per 100 g, P<0.001). TNFalpha was not significantly different between the groups. In both groups there was an inverse correlation between insulin sensitivity and serum leptin (r=-0.65, P<0.0001 for pooled subjects); in contrast, no significant relation was found between insulin sensitivity and norepinephrine or TNFalpha. In multivariate regression analysis, leptin emerged as the only significant predictor of insulin sensitivity (standardised coefficient=-0.59, P<0.001), independent of body fat mass, age and peak VO2. CONCLUSION: In moderate CHF, elevated leptin levels directly and independently predict insulin resistance. Elevated serum leptin levels could play a role in the impaired regulation of energy metabolism in CHF. In contrast to observations in other conditions, TNFalpha and norepinephrine are not related to insulin resistance in moderate CHF.

Adipose Tissue↗