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Dietary Intervention for Fatty Liver Disease: Fat or Carbohydrate Restriction?
Ryan MC, et al. Diabetes Care. 2007;30(5):1075-1080
The spectrum of nonalcoholic fatty liver disease (NAFLD) can range from asymptomatic accumulation of fat in the liver without inflammation, to non-alcoholic Steatohepatitis (NASH). Because NASH is an inflammatory condition, it ultimately leads to fibrosis and even end-stage liver disease in some. Increasing numbers of obese and diabetic individuals result in clinicians encountering NAFLD regularly.
Initial treatment recommended for NASH is weight loss. Major consensus groups (eg, American Heart Association, American Diabetes Association) have advocated a diet with less than 30% fat. Typically, however, fat restriction is compensated by an increase in dietary carbohydrate, which can induce deleterious metabolic consequences to insulin levels and triglycerides.
To study the impact of fat vs carbohydrate restriction, 52 obese individuals were given a calorie-restricted diet containing 15% protein. The remainder of calories was then divided as either 60% carbohydrate/25% fat or 40% carbohydrate/45% fat.
The amount of weight loss was equal in the two groups over 16 weeks. Serum alanine aminotransferase levels decreased significantly more in the group assigned to low carbohydrate, suggesting reduced fat-induced hepatic inflammation. The authors suggest that a carbohydrate restricted, moderately fat enhanced diet provides physiologic benefits for obese individuals compared to dietary advice currently recommended.
Motivational Interviewing to Enhance Weight Control in Diabetic Women
West DS, et al. Diabetes Care. 2007;30(5):1081-1087.
Motivational Interviewing (M-INT) is not a generic term, but rather a specific process of techniques that have proven successful in diverse health issues; fundamentally, it is based upon an exploration of a person's rationale for change, coupled with elucidation of their own ambivalence, looking into discrepancies between current behavior and core values/personal goals.
Overweight diabetic women (n = 217) were enrolled in an 18 month randomized controlled trial. All subjects participated in an intensive behavioral weight control program with guidance by a multidisciplinary team including psychologists, dietitians, exercise counselors, and diabetes educators to assist with caloric restriction (1200-1500 kcal/day). Half the group also received M-INT, administered as five individual sessions (45 minutes) at baseline, 3, 6, 9, and 12 months.
Both groups experienced weight loss, but the M-INT group lost more weight at each measurement point (eg, 4.8 kg vs 2.7 kg at 12 months). Although the A1c improvement seen in the M-INT group was superior at six months, by eighteen months, the groups were similar. The results of this data should have wide generalizability, because the study subjects were ethnically diverse (eg, 38% African American). Whether male subjects would enjoy similar benefits has not yet been studied.
One-stop Shopping for Osteoporosis Treatment
Black DM, et al. N Engl J Med. 2007;356:1809-1822.
Management of osteoporosis (OSPS) has evolved from daily treatment with bisphosphonates, to weekly or even monthly administration. There is some support for the concept that every step towards dosing parsimony improves likelihood of compliance, keeping in mind, however, that with treatment regimens employing infrequent dosing, each omissive error is also more consequential!
Zoledronic acid (ZDA) is a parenteral bisphosphonate (BIS), and is felt to work by similar mechanism to oral BIS (ie, alendronate, ibandronate, risedronate). The notoriously poor bioavailability of oral BIS requires strict administration techniques, without which absorption is severely compromised. As many as 50% of persons prescribed oral BIS have been documented to be non-adherent after a single year of use.
A double-blind placebo-controlled trial of ZDA in postmenopausal women with OSPS (n = 7,765) monitored new vertebral fractures and hip fractures over 36 months. ZDA was administered as a one-time 15-minute intravenous infusion of 5 mg each year for 3 years.
Over 3 years, ZDA reduced vertebral fractures by 70%, and hip fracture by 41%. Bone mineral density was improved. Markers of bone turnover were improved. The results attained equal or surpass those shown in clinical trials of oral BIS. One case of osteonecrosis was seen in the treatment group, but one was also seen in the placebo group. Although atrial fibrillation was seen more often in the ZDA group (mechanism unknown), adverse events associated with atrial fibrillation such as stroke were similar in both groups.
Post-stroke prevention of venous thromboembolism
Sherman DG, et al. Lancet. 2007;369:1347-1355
Unless prophylaxed, most post-stroke patients with hemiplegia develop deep venous thrombosis (DVT), and as many as 20% sustain pulmonary embolism (PE). Indeed, as many as 25% of early post-stroke deaths are attributable to PE.
Both low molecular weight heparin (LMWH) and unfractionated heparin (UHEP) are effective tools for prevention of venous thromboembolism, but a risk/benefit comparison of adequate size to provide conclusive evidence has been lacking.
Sherman, et al, performed a study on patients (n = 1762) with acute ischemic stroke who were unable to ambulate due to the stroke. Subjects were randomly assigned to enoxaparin 40 mg SQ daily (LMWH), or UHEP 5000 U SQ every 12 hours, both administered for 10 days. The primary endpoint was a composite of DVT, and PE (fatal and nonfatal). Compared to UHEP, LMWH reduced the primary endpoint by 43%, without any measurable difference in bleeding complications. Since enoxaparin is administered once daily, has greater efficacy than UHEP, and no greater bleeding risk, it should be preferred for prevention of venous thromboembolism.
Chronic Kidney Disease: Treatment Modality and Quality of Life
Kalender B, et al. Int J Clinical Practice. 2007;61(4):569-576.
It is not surprising that Chronic Kidney Disease (CKD) should exact a toll on quality of life (QOL). The studies on impact of treatment modality have been inconclusive, some indicating that continuous ambulatory peritoneal dialysis (CAPD) has less QOL detriment than hemodialysis (HMD), but others showing no difference. Kalender, et al evaluated CKD patients (n = 141) in comparison with healthy controls (n = 66) in reference to depression, malnutrition, inflammation (as measured by CRP and ferritin), CKD treatment modality, and their respective impact upon QOL, utilizing the SF-36 metric.
Overall, CAPD had QOL scores close to those of the control population. Depression was more common in HMD patients than CAPD also, and when depression was present in CAPD patients, the depression score was less (as measured by the Beck Depression Inventory).
Because malnutrition and inflammation were less frequent in the CAPD group, the authors posit that although HMD itself may be a culprit in detrimental QOL impact, malnutrition and inflammation may also play a role.
Hepatitis C and Risk for Lymphoma
Giordano T, et al. JAMA. 2007;297(18):2010-2017.
Although a minority of individuals who contract Hepatitis C (HEPc) spontaneously clear the virus (15-40%), most untreated individuals remain at risk for long-term consequences including chronic hepatitis, cirrhosis, and hepatic cancer.
The prevalence of HEPc in persons with nHOD is greater than the general population. Additionally, an association between HEPc and lymphoproliferative disorders has been bolstered by the observation of non-Hodgkin lymphoma (nHOD) regression subsequent to interferon treatment for HEPc.
US Veterans provide a population for studying the epidemiology of HEPc, since the prevalence of HEPc in this group is almost 5%, compared with 1.6% in the overall US population. National data from the US VA hospital system included 146,394 patients with HEPc, who were compared with 572,293 individuals negative for HEPc in this report by Giordano et al.
The hazard ratio for nHOD among persons with HEPc was 1.28 (28% greater incidence). There was also increased risk of Waldenstrom macroglobulinemia, which is also considered a low-grade lymphoma. No other hematologic malignancies were disproportionately represented. The authors conclude that this information supports a 20-30% increased risk for lymphoma among persons with HEPc.