OBJECTIVE Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis. RESULTS The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI). CONCLUSIONS Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.

Pharmacogenetic testing (PGT) is increasingly being used as a tool to guide clinical decisions. This article describes the development of an outpatient, pharmacist-led, pharmacogenetics consult clinic within internal medicine, its workflow, and early results, along with successes and challenges. A pharmacogenetics-trained pharmacist encouraged primary care physicians (PCPs) to refer patients who were experiencing side effects/ineffectiveness from certain antidepressants, opioids, and/or proton pump inhibitors. In clinic, the pharmacist confirmed the need for and ordered CYP2C19 and/or CYP2D6 testing, provided evidence-based pharmacogenetic recommendations to PCPs, and educated PCPs and patients on the results. Operational and clinical metrics were analyzed. In two years, 91 referred patients were seen in clinic (mean age 57, 67% women, 91% European-American). Of patients who received PGT, 77% had at least one CYP2C19 and/or CYP2D6 phenotype that would make conventional prescribing unfavorable. Recommendations suggested that physicians change a medication/dose for 59% of patients; excluding two patients lost to follow-up, 87% of recommendations were accepted. Challenges included PGT reimbursement and referral maintenance. High frequency of actionable results suggests physician education on who to refer was successful and illustrates the potential to reduce trial-and-error prescribing. High recommendation acceptance rate demonstrates the pharmacist’s effectiveness in providing genotype-guided recommendations, emphasizing a successful pharmacist–physician collaboration.

This study was designed to investigate the effect of soy protein inclusion in milk replacer diets for goat kids on protein, RNA, and DNA contents in small intestinal mucosa, on the importance of RNA biosynthesis from dietary RNA precursors for mucosal RNA synthesis, and on the activities of enzymes involved in nucleotide degradation in small intestinal mucosa. Diets were based on cow's milk. In the control group, 35% of the milk protein was replaced by casein (CN) protein, and in the soy group (SPAA), the same amount of milk protein was replaced by soy protein supplemented with essential AA known to be at lower concentrations in soy than in CN (Thr, Val, Ile, Leu, His, Lys, Met). Diets were isonitrogenous and isoenergetic. At 47 d of age, goats were harvested and samples of proximal, middle, and distal jejunal mucosa were collected 5 h after feeding 15N-labeled RNA from yeast (13 mg/kg of body weight). Growth and feed conversion did not differ between the control and SPAA kids. Mucosal protein concentrations were lower in the SPAA than the control kids. Concentrations of RNA and DNA did not differ between feeding groups, but in all kids mucosal RNA concentrations were higher in proximal than in middle and distal jejunum. Protein:RNA ratios were higher in the control than the SPAA kids and were lowest in proximal jejunum. Activities of alkaline phosphatase in enterocytes were higher in proximal than in middle and distal jejunum. Activities of mucosal xanthine oxidase were highest in distal jejunum and were higher in the SPAA than the control kids, especially in the middle and distal sites. The 15N-enrichment of mucosal RNA was higher in the control than the SPAA kids, especially in distal jejunum, and was lowest in distal jejunum. In contrast, 15N-enrichment of urea in plasma tended to be higher and Gly concentration in plasma was lower in the SPAA than the control kids. Data indicate that protein content and the protein:RNA ratio were lower in jejunal mucosa of goat kids fed milk replacer with partial replacement of CN protein by soy protein. These findings were accompanied by a lower level of reutilization of preformed dietary RNA precursors for RNA biosynthesis in jejunal mucosa and a higher activity of xanthine oxidase. Thus, feeding soy protein instead of CN protein reduced the incorporation of preformed dietary RNA precursors for RNA biosynthesis in the mucosa and activated key enzymes involved in nucleic acid breakdown.

Zinc metabolism and metallothionein induction in rat bone marrow were investigated during induced erythropoiesis. Redistribution of body zinc was measured with 65Zn after acute blood loss in rats fed zinc-restricted or zinc-adequate diets. Uptake of 65Zn by bone marrow was related to time after blood loss, metallothionein induction, and dietary zinc status. Increased 65Zn uptake by marrow of zinc-restricted rats suggests a minimal amount of zinc is necessary to support expansion of the erythrocytic compartment. Zinc induction of marrow metallothionein also occurred in rats in which anemia was produced using phenylhydrazine. Anemic rats which were administered zinc had higher concentrations of marrow metallothionein compared with control rats. Induction of marrow metallothionein by zinc in nonanemic rats required prior treatment with erythropoietin. Percoll fractionation showed marrow metallothionein was most abundant in erythroblasts. These experiments suggest metallothionein synthesis occurs in erythropoietin-sensitive precursor cells in the marrow in response to increased zinc accessibility.