Evaluation of serum 1,5 anhydroglucitol levels as a clinical test to differentiate subtypes of diabetes.

OBJECTIVE: Assignment of the correct molecular diagnosis in diabetes is necessary for informed decisions regarding treatment and prognosis. Better clinical markers would facilitate discrimination and prioritization for genetic testing between diabetes subtypes. Serum 1,5 anhydroglucitol (1,5AG) levels were reported to differentiate maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation. We evaluated serum 1,5AG in a range of diabetes subtypes as an adjunct for defining diabetes etiology. RESEARCH DESIGN AND METHODS: 1,5AG was measured in U.K. subjects with: HNF1A-MODY (n = 23), MODY due to glucokinase mutations (GCK-MODY, n = 23), type 1 diabetes (n = 29), latent autoimmune diabetes in adults (LADA, n = 42), and type 2 diabetes (n = 206). Receiver operating characteristic curve analysis was performed to assess discriminative accuracy of 1,5AG for diabetes etiology. RESULTS: Mean (SD range) 1,5AG levels were: GCK-MODY 13.06 microg/ml (5.74-29.74), HNF1A-MODY 4.23 microg/ml (2.12-8.44), type 1 diabetes 3.09 microg/ml (1.45-6.57), LADA 3.46 microg/ml (1.42-8.45), and type 2 diabetes 5.43 (2.12-13.23). Levels in GCK-MODY were higher than in other groups (P < 10(-4) vs. each group). HNF1A-MODY subjects showed no difference in unadjusted 1,5AG levels from type 2 diabetes, type 1 diabetes, and LADA. Adjusting for A1C revealed a difference between HNF1A-MODY and type 2 diabetes (P = 0.001). The discriminative accuracy of unadjusted 1,5AG levels was 0.79 for GCK-MODY versus type 2 diabetes and 0.86 for GCK-MODY versus HNF1A-MODY but was only 0.60 for HNF1A-MODY versus type 2 diabetes. CONCLUSIONS: In our dataset, serum 1,5AG performed well in discriminating GCK-MODY from other diabetes subtypes, particularly HNF1A-MODY. Measurement of 1,5AG levels could inform decisions regarding MODY diagnostic testing.

Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study.

BACKGROUND: The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well established and likely to contribute to cardioprotective benefits. OBJECTIVES: We aimed to determine the effect of moderate EPA and DHA intakes (<2 g EPA+DHA/d) on the plasma fatty acid profile, lipid and apolipoprotein concentrations, lipoprotein subclass distribution, and markers of oxidative status. We also aimed to examine the effect of age, sex, and apolipoprotein E (APOE) genotype on the observed responses. DESIGN: Three hundred twelve adults aged 20-70 y, who were prospectively recruited according to age, sex, and APOE genotype, completed a double-blind placebo-controlled crossover study. Participants consumed control oil, 0.7 g EPA+DHA/d (0.7FO), and 1.8 g EPA+DHA/d (1.8FO) capsules in random order, each for an 8-wk intervention period, separated by 12-wk washout periods. RESULTS: In the group as a whole, 8% and 11% lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO, respectively (P < 0.001): significant sex x treatment (P = 0.038) and sex x genotype x treatment (P = 0.032) interactions were observed, and the greatest triacylglycerol-lowering responses (reductions of 15% and 23% after 0.7FO and 1.8FO, respectively) were evident in APOE4 men. Furthermore, lower VLDL-cholesterol (P = 0.026) and higher LDL-cholesterol (P = 0.010), HDL-cholesterol (P < 0.001), and HDL2 (P < 0.001) concentrations were evident after fish-oil intervention. CONCLUSIONS: Supplements providing EPA+DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile. The results of the current trial, which used a prospective recruitment approach to examine the responses in population subgroups, are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females.

Detection of human herpesvirus 6 sequences in lymphoma tissues by immunohistochemistry and polymerase chain reactions.

We have analyzed one Hodgkin's and six non-Hodgkin's lymphomas for the presence of human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR) and antigens by immunohistochemistry. A large cell B-cell lymphoma and a T-cell lymphoma were positive for HHV-6 antigens by immunohistochemistry. Using PCR primers from the HHV-6 ZVH14 transforming DNA segment, all seven tumors were positive. EBV DNA was not detected by PCR using sequences from EBV internal repeat-3 region as primers. The data suggest an etiologic involvement of HHV-6 in some human lymphomas. Although all seven of the lymphoma tissues examined contained HHV-6 DNA, expression of HHV-6 antigens was observed in only two cases, suggesting that expression of proteins was not required for transformation.

Histochemical analysis of growth factor, fibronectin, and iron content of sickle cell leg ulcers.

To better understand the pathogenesis and slow healing of sickle cell leg ulcers, we analyzed tissues for their content of iron and their immunohistochemical level of basic fibroblast growth factor, transforming growth factor-beta, and fibronectin. Debrided leg ulcer tissue from seven patients with sickle cell anemia were used. All sections stained strongly for basic fibroblast growth factor. The reactions to iron and fibronectin were variable (trace to 4+, 0 to 3+, respectively), and there was weak or negative immunohistochemical staining for transforming growth factor-beta. These findings suggest the possibility that iron and/or a low content of transforming growth factor-beta and fibronectin may play a role in the chronicity of these lesions. Conversely, reducing tissue iron and/or applying transforming growth factor-beta or fibronectin topically may promote the healing of sickle cell leg ulcers.

Studies in sickle cell anemia: Preliminary observation on gastrointestinal digestion and absorption.

This study investigates certain aspects of the adequacy of digestion, absorption, motility, and morphology of the gastrointestinal tract of children with sickle cell anemia. Medical literature contains a paucity of information on this subject.

A new look at the protection of hemoglobin AS and AC genotypes against plasmodium falciparum infection: a census tract approach.

A total of 4,097 randomly selected children under 5 years in Accra, Ghana were investigated for Hb type, malarial parasite species, and parasite density. Even though malarial infection rates in this metropolitan population were lower as compared to holoendemic areas, the differential survival of Hb S carriers was confirmed. In addition, similar but less pronounced survival effects were seen in Hb C heterozygotes. Hb S carriers had the highest infection rates. More females than males were infected. Individuals with a moderate parasite count (less than 50,000/ml) were seen more commonly amoung AS and AC individuals as compared to AA controls. It is postulated that heterozygotes have a better immunological defense against the deleterious effects of P. falciparum infection because persistent parasitemia stimulates antibody production.