Biomedical subjects

B D Mitchell

Publications and source records attributed to B D Mitchell.

112 records · Page 7Linked to original sources

PubMedDate not supplied

Molecular scanning for mutations in the insulin receptor substrate-1 (IRS-1) gene in Mexican Americans with Type 2 diabetes mellitus.

BACKGROUND: Insulin receptor substrate-1 (IRS-1) is an endogenous substrate for the insulin receptor tyrosine kinase, which plays an important role in insulin signaling. Mutations in the IRS-1 gene are associated in some populations with obesity and Type 2 diabetes. METHODS: To determine whether variation in the IRS-1 gene contributes to genetic susceptibility to insulin resistance and Type 2 diabetes in Mexican Americans, the entire coding region of the IRS-1 gene was screened for variation in 31 unrelated subjects with Type 2 diabetes using single-stranded conformational polymorphism analysis (SSCP) and dideoxy sequence analysis. Variants encoding amino acid substitutions were genotyped in 27 unrelated nondiabetic Mexican Americans and in all family members of subjects containing these variants, and association analyses were performed. To trace the ancestral origins of the variants, Iberian Caucasians and Pima Indians were also genotyped. RESULTS: Eight single base changes were found: four silent polymorphisms and four missense mutations (Ala94Thr, Ala512Pro, Ser892Gly and Gly971Arg). Allele frequencies were 0.009, 0.017, 0.017 and 0.043, respectively. There were no significant associations of any of these variants with diabetes, glucose or insulin levels during an oral glucose tolerance test, or with body mass index (BMI) in Mexican American families except for a modest association between the Ala94Thr variant and decreased BMI (30.4 kg/m(2) vs 24.0 kg/m(2); p=0.035). None of these four missense mutations were detected in Pima Indians. In Iberian Caucasians, neither Ala94Thr nor Ser892Gly were detected, and Ala512Pro was detected in only 0/60 diabetic patients and 1/60 nondiabetic controls. Gly971Arg was relatively more common in Iberian Caucasians with 12/58 diabetic patients and 7/60 nondiabetic controls being heterozygous for this variant (p=0.21 for comparison between diabetic and nondiabetic subjects). CONCLUSIONS: Ala94Thr, Ala512Pro and Ser892Gly mutation are rare in the populations studied. Gly971Arg, is more common in Mexican Americans and Caucasians, but is not a major contributor to genetic susceptibility to Type 2 diabetes.

Adult↗

PubMedDate not supplied

Diabetes and coronary heart disease risk in Mexican Americans.

Mexican Americans have a high prevalence of diabetes relative to non-Hispanic whites, but paradoxically experience a lower prevalence of myocardial infarction and lower cardiovascular mortality (at least in men). To determine whether Mexican Americans might be more resistant to the atherogenic effects of diabetes than non-Hispanic whites, we examined the associations between diabetes and myocardial infarction and selected coronary heart disease (CHD) risk factors in these two ethnic groups. The study population consisted of 5149 Mexican Americans and non-Hispanic whites who were 25 to 64 years old and recruited from the San Antonio Heart Study, a population-based study of cardiovascular risk factors and diabetes conducted between 1979 and 1988. Diabetic men were more than twice as likely to have an electrocardiography (ECG)-documented myocardial infarction than were nondiabetic men, while diabetic women were more than three times as likely to have a myocardial infarction than were nondiabetic women. In both sexes the association between myocardial infarction and diabetes was nearly identical between the two ethnic groups. In both ethnic groups diabetes was also more strongly associated with conventional CHD risk factors (e.g., triglycerides, systolic blood pressure, and high-density-lipoprotein cholesterol) in women than in men. Furthermore, these associations were at least as strong, if not stronger, in Mexican Americans as in non-Hispanic whites. Thus, these data provide no evidence to suggest that Mexican Americans are resistant to the lipid-altering effects of diabetes. We conclude that the protective effect against CHD conferred by Mexican American ethnicity may be obscured in part by the high prevalence of diabetes in this ethnic group.

Adult↗

PubMedDate not supplied

Microalbuminuria. Potential marker for increased cardiovascular risk factors in nondiabetic subjects?

Microalbuminuria is associated with progression to renal disease in insulin-dependent diabetes and with increased mortality in noninsulin-dependent diabetes. In contrast, few studies have addressed the effect of microalbuminuria on cardiovascular risk in nondiabetics. We, therefore, determined the level of microalbuminuria in 316 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. Microalbuminuria (greater than or equal to 30 mg/l) was found in 42 of these 316 subjects (13%). Subjects with microalbuminuria had significantly higher blood pressure, triglyceride concentration, sum of insulin concentrations during a glucose tolerance test, and prevalence of hypertension and of self-reported myocardial infarction than subjects without microalbuminuria. When subjects with hypertension were excluded (n = 27), normotensive subjects with microalbuminuria (n = 31) still had significantly higher triglyceride concentrations and insulin sum than normotensive subjects without microalbuminuria (n = 258), suggesting that an increased atherogenic risk factor pattern exists even in normotensive subjects with microalbuminuria. Microalbuminuria may be a marker for cardiovascular risk, although it is not certain whether microalbuminuria causes these metabolic changes or results from some metabolic disturbance such as insulin resistance.

Adult↗

PubMedDate not supplied

Parental history of diabetes is associated with increased cardiovascular risk factors.

Serum insulin concentrations are higher in persons with a positive parental history of diabetes than in persons without such a history. Since hyperinsulinemia is associated with both an increased prevalence of hypertension and an atherogenic pattern of serum lipids and lipoproteins, we hypothesized that among nondiabetic persons, a parental history of diabetes would be associated with an atherogenic pattern of cardiovascular risk factors. In the San Antonio Heart Study, a population-based study of cardiovascular disease and diabetes, we examined 549 nondiabetic persons with a parental history of diabetes and 1167 nondiabetic persons without such a history. Compared to persons without a parental history of diabetes, those with such a history had a more atherogenic pattern of cardiovascular risk factors, including higher body mass index, higher systolic and diastolic blood pressures, higher serum insulin and triglyceride concentrations, and lower levels of high density lipoprotein cholesterol. After adjustment for serum insulin concentration, body mass index, and waist-to-hip ratio, the differences in lipids, lipoproteins, and blood pressure between the two parental history groups were no longer statistically significant. Since persons with a parental history of diabetes are more likely to be prediabetics, the present results suggest that prediabetics have an increased risk of coronary heart disease even before they become diabetic. This phenomenon may help explain why the duration of clinical diabetes is only weakly associated with the risk of coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗