The role of HLA class II alleles in genetic predisposition to insulin dependent diabetes mellitus (IDDM) was examined by PCR/oligonucleotide probe typing of 42 Mexican-American IDDM families derived from Hispanic Caucasians and Native Americans. All high risk haplotypes (HLA-DR3 and DR4) were of European origin while the most strongly protective haplotype (DRB1*1402) was Native American. Of the 16 DR-DQ DR4 haplotypes identified, only those bearing DQB1*0302 conferred risk; the DRB1 allele, however, also markedly influenced IDDM risk. The general pattern of neutral and protective haplotypes indicates that the presence of Asp-57 in the HLA-DQ beta chain does not confer IDDM protection per se and indicates that both DRB1 and DQB1 influence IDDM susceptibility as well as protection.
Women in the United States have a 12.3% estimated lifetime risk for developing breast cancer (i.e., 1 in 8 women). 1 In 2009, an estimated 194,290 cases of invasive breast cancer (192,370 women and 1919 men) and 62,280 cases of female carcinoma in situ of the breast will be diagnosed in the United States, with 40,610 deaths from invasive breast cancer predicted. 2 However, mortality from breast cancer has decreased slightly, attributed partly to mammographic screening. 3 The NCCN Breast Cancer Screening and Diagnosis Panel designed these practice guidelines to fa-The NCCN
These results suggest that type II diabetic patients have intracellular Mg2+ deficiency and that Mg deficiency may be a key factor in leading to enhanced platelet reactivity in type II diabetes. Therefore, Mg supplementation may provide a new therapeutic approach to reducing vascular disease in patients with diabetes.
The prevalence of hypomagnesemia and hypermagnesemia among hospitalized patients was studied by determining magnesium levels in 621 serum samples randomly selected from those submitted to the clinical chemistry laboratory for a biochemical test panel. The reference range for serum magnesium was established in this study as 1.2 to 1.9 mEq/L from measurements of serum magnesium on 341 healthy volunteers. Hypomagnesemia (less than 1.2 mEq/L) was present in 68 patients or 11.0%, and hypermagnesemia (greater than 1.9 mEq/L) occurred in 58 patients or 9.3%. The degree of association between hypomagnesemia and hypocalcemia was assessed by measuring serum magnesium on a separate group of 61 patients with hypocalcemia (corrected calcium less than 8.6 mg/dL). Hypomagnesemia was present in 23.3% of patients hypocalcemic in the absence of renal failure; this proportion was higher significantly than the 11.0% who were hypomagnesemic in the hospitalized patient group (P less than 0.025).
Susceptibility to IDDM has been associated with specific alleles at the HLA class II loci in a variety of human populations. Previous studies among Mexican-Americans, a group ancestrally derived from Native Americans and Hispanic whites, showed that the DR4 haplotypes (DRB1*0405-DQB1*0302 and DRB1*0402-DQB1*0302) and the DR3 haplotype (DRB1*0301-DQB1*0201) were increased among patients and suggested a role for both DR and DQ alleles in susceptibility and resistance. Based on the analysis of 42 Mexican-American IDDM families and ethnically matched control subjects by polymerase chain reaction/sequence-specific oligonucleotide probe typing, we report an association of IDDM with the DPB1 allele, *0301 (relative risk = 6.6; P = 0.0012) in this population. The analysis of linkage disequilibrium patterns in this population indicates that the observed increased frequency in DPB1*0301 among patients cannot be attributed simply to linkage disequilibrium with high-risk DR-DQ haplotypes. These data suggest that in addition to alleles at the DRB1 and DQB1 loci, polymorphism at the DPB1 locus may also influence IDDM risk.
To further elucidate the mechanism of impaired gallbladder emptying in diabetics with and without neuropathy, gallbladder function was assessed by ultrasonography following a medium-chain triglyceride (lipomul, 1.5 mg/kg) infusion into the duodenum and compared to that during intravenous infusion of cholecystokinin in diabetic women. Results were compared with five healthy control women. Mean (+/- SD) maximal percent gallbladder volume in diabetics following lipomul was reduced to 49 +/- 8% and after intravenous cholecystokinin to 47 +/- 9%, which was less than those in controls, 21 +/- 9% and 24 +/- 6%, respectively, but not significantly different. Further analysis of gallbladder emptying to lipomul differentiated two subgroups of diabetics: one subgroup (N = 5) had emptying comparable to controls (responders), while the other (N = 5) had very modest emptying (nonresponders). Two of the patients in the latter group had normal gallbladder emptying during exogenous cholecystokinin and their response would be compatible with visceral neuropathy. Blood levels of cholecystokinin, measured by bioassay, following lipomul and exogenous cholecystokinin were similar in controls and diabetics. Presence of diabetic neuropathy did not correlate with impaired gallbladder emptying. Follow up at 6 and 12 months of the three nonresponder diabetics revealed that no gallstones had developed and that two of them became responders to exogenous cholecystokinin.(ABSTRACT TRUNCATED AT 250 WORDS)
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