Severe Liver Injury Associated With High-Dose Atorvastatin Therapy.

Statins are recommended for first-line management of elevated cholesterol in the primary and secondary prevention of atherosclerotic cardiovascular disease. Statins may occasionally be associated with mild transaminase elevations but can also result in life-threatening liver injury. Atorvastatin is the most common cause of clinically significant liver injury in this drug class. We report a case of severe, asymptomatic liver injury in a hepatocellular pattern in a 71-year-old man occurring within 3 months of switching from simvastatin to high-intensity atorvastatin therapy. Hepatitis improved rapidly with cessation of atorvastatin and did not recur after resuming simvastatin.

Marked lowering of high-density lipoprotein cholesterol levels due to high dose bexarotene therapy.

CONTEXT: Bexarotene is a retinoid X receptor agonist, which is currently used for the treatment of cutaneous T-cell lymphoma (CTCL). It is known to induce central hypothyroidism as well as dyslipidemia including elevation of triglycerides (TG) and low-density lipoprotein cholesterol along with slight lowering of high-density lipoprotein cholesterol (HDL-C). Marked lowering of HDL-C has never been previously reported in bexarotene-treated patients and whether it is related to hypothyroidism remains unclear. CASE REPORT: A 49-year-old African female with a history of CTCL on treatment with bexarotene of 300 mg/d, presented with serum total cholesterol level of 249 mg/dL (6.4 mmol/L), TG level of 92 mg/dL (1.03 mmol/L), HDL-C level of 78 mg/dL (2.02 mmol/L), thyroid stimulating hormone (TSH) of 0.68 µIU/mL, and free thyroxine level of 0.5 ng/dL. Six months later, on increasing the bexarotene dose to 600 mg daily, serum TG increased to 310 mg/dL (3.5 mmol/L) and HDL-C dropped to 3 to 5 mg/dL (0.077-0.13 mmol/L), whereas the TSH was undetectable (0.01 µIU/mL). Despite adequate levothyroxine replacement to 225 µg daily resulting in free thyroxine levels up to 1.5 ng/dL, HDL-C remained extremely low of 4 to 9 mg/dL (0.103-0.233 mmol/L). Bexarotene was discontinued due to poor response of CTCL, 3 months after which her HDL-C levels returned to baseline of 80 to 90 mg/dL (2.07-2.33 mmol/L). CONCLUSIONS: High dose bexarotene can markedly lower HDL-C levels, which normalize on discontinuation of the drug. Lowering of HDL-C with bexarotene may be due to an increase in cholesterol ester transfer protein activity and appears to be independent of central hypothyroidism.

Effect of a high-fiber diet compared with a moderate-fiber diet on calcium and other mineral balances in subjects with type 2 diabetes.

OBJECTIVE: High levels of dietary fiber, especially soluble fiber, are recommended to lower serum cholesterol levels and improve glycemic control in patients with type 2 diabetes. It is not clear, however, how high levels of fiber affect mineral balance. RESEARCH DESIGN AND METHODS: In a randomized crossover study, 13 patients with type 2 diabetes were fed a high-fiber (50 g total and 25 g soluble fiber) and a moderate-fiber (24 g total and 8 g soluble fiber) diet of the same energy, macronutrient, calcium, magnesium, and phosphorus content for 6 weeks each. Intestinal calcium absorption was determined by fecal recovery of (47)Ca. Stool weight and mineral content were assessed during 3 days, and 24-h urinary mineral content and serum chemistry were assessed over 5 days at the end of each phase. The results were compared by repeated-measures ANOVA. RESULTS: Compared with the moderate-fiber diet, the high-fiber diet increased stool weight (165 +/- 53 vs. 216 +/- 63 g/day, P = 0.02) and reduced 24-h urinary calcium (3.3 +/- 1.7 vs. 2.4 +/- 1.2 mmol/day, P = 0.003) and phosphorus (29.2 +/- 5.5 vs. 26.0 +/- 3.2 mmol/day, P = 0.003) excretion and serum calcium concentration (2.33 +/- 0.06 vs. 2.29 +/- 0.07 mmol/l, P = 0.04). Calcium absorption, stool calcium, magnesium, and phosphorus content and serum phosphorus concentration were not significantly different with the two diets. CONCLUSIONS: A high-fiber diet rich in soluble fiber has a small impact on calcium and phosphorus balance in subjects with type 2 diabetes. It may be prudent to ensure adequate intake of calcium and other minerals in individuals consuming a high-fiber diet.

Effect of high-carbohydrate or high-cis-monounsaturated fat diets on blood pressure: a meta-analysis of intervention trials.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is recommended to manage blood pressure. The DASH diet is low in saturated fat, but it is not clear whether saturated fat should be preferentially replaced with carbohydrate or unsaturated fat, especially cis-monounsaturated fat. OBJECTIVE: A meta-analysis of intervention studies comparing high-carbohydrate and high-cis-monounsaturated fat diets was conducted to increase understanding of the effect of carbohydrate and cis-monounsaturated fat on blood pressure. DESIGN: For study diets to be included in the analysis, they had to be isoenergetic, and the subjects' body weight had to remain stable. Ten studies (6 randomized crossover, 1 randomized parallel, and 3 nonrandomized) met the inclusion criteria. RESULTS: According to the random-effects model, which incorporates between-study variation to estimate the overall effect, diets rich in carbohydrate resulted in significantly higher systolic blood pressure [x(-) difference: 2.6 (95% CI: 0.4, 4.7) mm Hg; P=0.02] and diastolic blood pressure [1.8 (0.01, 3.6) mm Hg; P=0.05] than did diets rich in cis-monounsaturated fat. When the meta-analysis was limited to randomized crossover studies, both systolic [1.3 (-0.3, 2.9) mm Hg; P=0.11] and diastolic [0.9 (-0.2, 2.1) mm Hg; P=0.11] blood pressure were higher with a high-carbohydrate than with a high cis-monounsaturated fat diet, but the differences were not significant. CONCLUSIONS: Diets rich in carbohydrate may be associated with slightly higher blood pressure than diets rich in cis-monounsaturated fat. However, the magnitude of the difference may not justify making recommendations to alter the carbohydrate and cis-monounsaturated fat content of the diet to manage blood pressure.

Review: long-term impact of bariatric surgery on body weight, comorbidities, and nutritional status.

CONTEXT: The number of patients who undergo Roux-en-Y gastric bypass (RYGB) and gastric banding (GB) surgeries has increased dramatically over the past decade, yet the long-term impact of these surgeries on body weight, comorbidities, and nutritional status remains unclear, as do the mechanisms of weight regain. EVIDENCE ACQUISITION: The articles were found via PubMed searches. To review the impact of bariatric surgery on weight maintenance and comorbidities, only articles with a postoperative follow-up of 3 yr or longer were included. The articles on nutritional status had a follow-up of 12 months or longer. CONCLUSIONS: RYGB and GB surgeries lead to substantial weight loss in individuals with morbid obesity. However, significant weight regain occurs over the long term, and according to the only well-designed prospective controlled study, the improvement in comorbidities associated with weight loss mitigates in the long term on weight regain. There is some evidence from a retrospective study that RYGB surgery is associated with a modest decrease in long-term mortality. These results remain to be substantiated by well-designed, long-term, randomized and prospective controlled studies. The mechanisms that lead to weight regain need to be further examined and may include increase in energy intake due to enlargement of stoma and adaptive changes in the levels of gut and adipocyte hormones such as ghrelin and leptin, which regulate energy intake; decrease in physical activity; changes in energy expenditure; and other factors. In addition to weight regain, RYGB surgery is associated with frequent incidence of iron, vitamin B12, folate, calcium, and vitamin D deficiency, which requires regular supplementation and monitoring.