Search PubMed⌕ Search

Biomedical subjects

K H Gabbay

Publications and source records attributed to K H Gabbay.

96 records · Page 6Linked to original sources
PubMedDate not supplied

Linkage analyses in type I diabetes mellitus using CASPAR, a software and statistical program for conditional analysis of polygenic diseases.

We have developed software and statistical tools for linkage analysis of polygenic diseases. We use type I diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) as our model system. Two susceptibility loci (IDDM1 on 6p21 and IDDM2 on 11p15) are well established, and recent genome searches suggest the existence of other susceptibility loci. We have implemented CASPAR, a software tool that makes it possible to test for linkage quickly and efficiently using multiple polymorphic DNA markers simultaneously in nuclear families consisting of two unaffected parents and a pair of affected siblings (ASP). We use a simulation-based method to determine whether lod scores from a collection of ASP tests are significant. We test our new software and statistical tools to assess linkage of IDDM5 and IDDM7 conditioned on analyses with 1 or 2 other unlinked type I diabetes susceptibility loci. The results from the CASPAR analysis suggest that conditioning of IDDM5 on IDDM1 and IDDM4, and of IDDM7 on IDDM1 and IDDM2 provides significant benefits for the genetic analysis of polygenic loci.

Alleles↗
PubMedDate not supplied

Glycosylation of variant hemoglobins in normal and diabetic subjects.

The extent of in vivo glycosylation of variant hemoglobins was examined in individuals with S-, C-, and D-trait. Chromatographic estimates of glycosylation for nondiabetic individuals with S-trait were significantly lower than those for nondiabetic black subjects with normal hemoglobin (P < 0.001). However, chemical determinations of glycosylation (thiobarbituric acid or TBA technique) were similar for these groups (P > 0.10). The chromatographic elution pattern of hemoglobin S (HbS) was determined, and on this basis an adjustment procedure was performed for chromatographic data. A regression line was calculated for the relationship between chromatographic and colorimetric estimates of glycosylated hemoglobin in S-trait individuals with and without diabetes. The slope of this line was significantly different (P < 0.001) from that for the relationship in individuals with normal hemoglobin. However, after adjustment of chromatographic values from S-trait individuals, the slopes were similar (P < 0.10). Findings from individuals heterozygous for HbC and D were similar to those for individuals with S-trait. These data indicate that the extent of glycosylation of HbS, C, and D is similar to that of HbA in both the normoglycemic and hyperglycemic range. The TBA technique is the most direct method for determining the extent of glycosylation in individuals with HbS, C, or D. However, adjustment of column chromatographic values is feasible.

Adult↗
PubMedDate not supplied

Hyperglycemia and plasma lipid levels: covariations in insulin-dependent diabetes.

Longitudinal relationships of plasma lipids with parameters of blood glucose control were studied in 124 young insulin-dependent diabetic patients who had multiple, simultaneous determinations of these parameters during a 1-yr period. Fluctuations in hemoglobin A1, a cumulative measure of blood glucose control, correlated with fluctuations in total cholesterol (r = 0.19, P less than 0.001) and low-density lipoprotein-cholesterol (r = 0.17, P less than 0.001). Similarly, fluctuations in fasting blood glucose correlated with those in total cholesterol (r = 0.20, P less than 0.001), very low-density lipoprotein-cholesterol (r = 0.13, P = 0.002), and total triglyceride (r = 0.23, P less than 0.001). These data indicate covariation between plasma lipid and blood glucose control parameters and suggest that poor blood glucose control contributes to the excess risk of coronary heart disease in insulin-dependent diabetes mellitus.

Adolescent↗
PubMedDate not supplied

Umbilical cord glycosylated hemoglobin in infants of diabetic mothers: relationships to neonatal hypoglycemia, macrosomia, and cord serum C-peptide.

Relationships of neonatal glycemia and birthweight to antecedent fetal glycemia and insulinemia have been examined in the offspring of 63 insulin-dependent diabetic and 29 nondiabetic mothers. Glycosylated hemoglobin levels in maternal and cord blood were measured by the thiobarbituric acid (TBA) colorimetric technique to estimate antecedent fetal and maternal glycemia; cord serum C-peptide was assayed to estimate fetal insulinemia. Glycosylated hemoglobin levels were significantly elevated in the diabetic mothers and their offspring as compared with controls (P less than 0.001), and maternal and cord blood levels were highly correlated in the diabetic group (r = 0.61, P less than 0.001). Cord serum C-peptide and glycosylated hemoglobin levels tended to be associated (r = 0.43, P less than 0.10). Hypoglycemic infants of diabetic mothers (IDM) had significantly higher glycosylated hemoglobin levels (A443 nm/10 mg hemoglobin hemolysate) in cord blood (0.173 +/- 0.009) than did IDM without hypoglycemia (0.153 +/- 0.005, P less than 0.01). Macrosomic and nonmacrosomic IDM, on the other hand, did not differ as to their glycosylated hemoglobin levels (0.162 +/- 0.005 versus 0.161 +/- 0.006, respectively). The occurrence of hypoglycemia was not associated with that of macrosomia (X2 = 0.24, P greater than 0.10). These data strongly suggest that neonatal hypoglycemia is the result of maternal hyperglycemia in pregnancy and consequent fetal hyperglycemia and hyperinsulinemia. However, maternal hyperglycemia in late pregnancy may not be a sufficient explanation for the development of macrosomia in IDM.

Blood Glucose↗