Biomedical subjects

Mark I McCarthy

Publications and source records attributed to Mark I McCarthy.

57 records · Page 4Linked to original sources

PubMed2002

Delayed metabolic and thermogenic response to a mixed meal in normoglycemic European women with previous gestational diabetes.

We assessed postprandial thermogenesis (PPT) for 3 h following a mixed meal in 29 normoglycemic European women with previous gestational diabetes (GDM), compared with 37 control women. Given the potential role of catecholamines and insulin in the regulation of PPT, we assessed insulin and catecholamine responses to the meal. There was no significant difference between the two groups in resting energy expenditure, PPT (although lower in the GDM group), or catecholamine levels. However, we observed a difference in the shape of the PPT curve between groups, and by applying a mathematical model, there was a consistent delay in PPT, insulin, and noradrenaline responses to the meal in the GDM group (T: fitted time constant, geometric mean (95% confidence interval), T(PPT) 58 (47-72) vs. 42 (37-48) min, P = 0.006; T(ins) 32 (28-37) vs. 22 (19-27) min, P = 0.002; T(NA) 30 (23-38) vs. 18 (14-23) min, P = 0.01, respectively). Fidgeting activity during the study was assessed by a novel technique and was lower in the GDM group, resting [427 (381-477) vs. 511 (466-560) kJ/min, P = 0.02] but not postprandially. These delayed PPT, insulin, and noradrenaline responses to the meal in post-GDM women represent early metabolic changes. The decrease in fidgeting activity while resting, observed in the post-GDM group, may have physiological significance for energy balance.

Adult↗

PubMed2002

Association studies of genetic variation in the WFS1 gene and type 2 diabetes in U.K. populations.

Mutations in the WFS1 gene cause beta-cell death, resulting in a monogenic form of diabetes known as Wolfram syndrome. The role of variation in WFS1 in type 2 diabetes susceptibility is not known. We sequenced the WFS1 gene in 29 type 2 diabetic probands and identified 12 coding variants. We used 152 parent-offspring trios to look for familial association; the R allele at residue 456 (P = 0.04) and the H allele at residue 611 (P = 0.05) as well as the R456-H611 haplotype (P = 0.032) were overtransmitted to affected offspring from heterozygous parents. In a further cohort of 327 type 2 diabetic subjects and 357 normoglycemic control subjects, the H611 allele and the R456-H611 haplotype were present in more type 2 diabetic subjects than control subjects (one-tailed P = 0.06 and P = 0.023, respectively). In a combined analysis, the H611 allele was present in 60% of all diabetes chromosomes and 55% of all control chromosomes (odds ratio [OR] 1.24 [95% CI 1.03-1.48], P = 0.02), and the R456-H611 haplotype was significantly more frequent in type 2 diabetic subjects than in control subjects (60 vs. 54%, OR 1.29 [95% CI 1.08-1.54], P = 0.0053). Our results provide the first evidence that variation in the WFS1 gene may influence susceptibility to type 2 diabetes.

Adult↗

PubMed2001

Evidence for linkage of stature to chromosome 3p26 in a large U.K. Family data set ascertained for type 2 diabetes.

We have analyzed data from 573 pedigrees from the United Kingdom for evidence for linkage to loci influencing adult stature. Our data set comprised 1,214 diabetic and 163 nondiabetic siblings for whom height data were available. We used variance-components analysis implemented in GENEHUNTER 2 and a modification of the Haseman-Elston regression method, HE-COM. We found evidence for a locus on 3p26 (LOD score 3.17) influencing height in this adult sample, with less-significant evidence for loci on chromosomes 7, 10, 15, 17, 19, and 20. Our findings extend similar recent studies in Scandinavian and Quebecois populations, adding further evidence that height is indeed under the control of multiple genes.

Adult↗