Effects of skim milk powder enriched with glycomacropeptide and G600 milk fat extract on frequency of gout flares: a proof-of-concept randomised controlled trial. Randomized controlled trial on lifestyle modification in hypertensive patients. Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: results of a phase II randomized study. A multi-institute case-control study on the risk factors of developing pancreatic cancer. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Early lifestyle intervention in patients with non-insulin-dependent diabetes mellitus and impaired glucose tolerance. Effects of lifestyle modifications on patients with type 2 diabetes: the Japan Diabetes Complications Study (JDCS) study design, baseline analysis and three year-interim report. Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1).
Previous laboratory studies have identified two dairy fractions, glycomacropeptide (GMP) and G600 milk fat extract (G600), with anti-inflammatory effects in models of acute gout. The aim of this proof-of-concept clinical trial was to test the hypothesis that daily intake of skim milk powder (SMP) enriched with GMP and G600 can prevent gout flares.
                This was a 3-month randomised double-blind controlled trial of milk products for prevention of gout flares. One hundred and twenty patients with recurrent gout flares were randomised to one of three arms: lactose powder control, SMP control and SMP enriched with GMP and G600 (SMP/GMP/G600). The primary end point was change in the frequency of gout flares using a daily flare diary measured monthly for 3 months.
                The frequency of gout flares reduced in all three groups over the 3-month study period compared with baseline. Over the 3-month study period there was a significantly greater reduction in gout flares in the SMP/GMP/G600 group (analysis of covariance p(group)=0.031, Tukey post hoc test compared with lactose control, p=0.044). Following treatment with SMP/GMP/G600 over the 3-month period, greater improvements were also observed in pain and fractional excretion of uric acid, with trends to greater improvement in tender joint count. Similar adverse event rates and discontinuation rates were observed between the three groups.
                This is the first reported controlled trial of dietary intervention in patients with gout, and suggests that SMP enriched with GMP and G600 may reduce the frequency of gout flares. The authors examined the effects of a comprehensive lifestyle modification intervention on blood pressure (BP) and other cardiovascular risk factors in hypertensive patients. A total of 70 participants were randomly placed into either a lifestyle intervention or a control group. Four education classes and individual counseling sessions were held for the intervention group. Participants in the control group were provided with routine outpatient services and were asked to maintain their usual lifestyle. Data were gathered at baseline and at the end of 6 months. At the end of 6 months, BP, body weight, body mass index, waist circumference, and fasting lipids, apart from high-density lipoprotein cholesterol, significantly declined in the intervention group. Healthpromoting lifestyle scores of the intervention group had increased significantly compared to those of the control group. In conclusion, the results demonstrate the feasibility of comprehensive lifestyle modification and show its beneficial effects. To assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase.
                Forty-one patients were randomized to undergo 12-14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded.
                The mean plasma urate level was reduced to <or=6 mg/dl within 6 hours in all dosage groups, and this was sustained throughout the treatment period in the 8 mg and 12 mg dosage groups. The most effective dosage was 8 mg every 2 weeks. Twenty-six patients received all protocol doses. The percentage of the patients in whom the primary efficacy end point (plasma urate <6 mg/dl for 80% of the study period) was achieved ranged from 50% to 88%. Gout flares occurred in 88% of the patients. The majority of adverse events (excluding gout flare) were unrelated to treatment and were mild or moderate in severity. Infusion-day adverse events were the most common reason for study withdrawal (12 of 15 withdrawals). There were no anaphylactic reactions. Antipegloticase antibody, present in 31 of 41 patients, was associated with reduced circulating half-life of pegloticase in some patients.
                Pegloticase, administered in multiple doses, was effective in rapidly reducing and maintaining plasma urate levels at <or=6 mg/dl in most patients in whom conventional therapy had been unsuccessful due to lack of response, intolerability, or contraindication. A multi-institute, hospital-based, case-control study on pancreatic cancer was carried out to examine its association with preceding diseases, cigarette smoking, alcohol drinking and dietary factors. Analyses were based on 124 newly diagnosed exocrine pancreatic cancer cases and sex-, age- and institute-matched hospital controls in seven hospitals in Japan. Cigarette smoking showed a positive association with the risk of developing pancreatic cancer. Especially among smokers, a risk enhancing effect of involuntary/passive smoking prior to twenty years of age was observed (P < 0.05). No consistent associations were found with coffee, black tea or alcohol consumption. Among dietary factors, favoring food of a salty taste and drinking green tea five cups per day or more were positively associated with the risk. Drinking milk and eating fish everyday were inversely associated with the risk. This 5-yr study assessed urate-lowering and clinical efficacy and safety of long-term febuxostat therapy in subjects with gout. The primary efficacy end-point was reduction to and maintenance of serum urate (sUA) levels < 6.0 mg/dl.
                Subjects who completed a previous 28-day study were entered into an open-label extension study and initially received febuxostat 80 mg daily. Between Weeks 4 and 24, dosing could be adjusted to febuxostat 40 or 120 mg. All subjects received gout flare prophylaxis during the first 4 weeks. Gout flares were recorded and treated throughout the study, and sUA, baseline tophi and safety were monitored.
                Among 116 subjects initially enrolled, dose adjustments were made for 44 (38%) subjects. As a result, 8 subjects received febuxostat 40 mg, 79 received 80 mg, and 29 received 120 mg daily maintenance dose. At 5 yrs, 93% (54/58) of the remaining subjects had sUA < 6.0 mg/dl. Fifty-eight subjects (50%) discontinued prematurely; 38 did so in the first year. Thirteen subjects withdrew due to an adverse event. Sustained reduction of sUA was associated with nearly complete elimination of gout flares. In 26 subjects with a tophus at baseline, resolution was achieved in 69% (18/26) by last visit on study drug at any point during the study (Final Visit). There were no deaths reported during the study.
                Long-term treatment with febuxostat resulted in durable maintenance of sUA < 6.0 mg/dl for most subjects. There was nearly complete abolition of gout flares in patients completing the study. Baseline tophi resolved in a majority of subjects. Non-insulin-dependent diabetes mellitus (NIDDM) is preceded by impaired glucose tolerance (IGT) lasting for years before manifesting as overt hyperglycaemia. Both genetic and environmental factors contribute to the development of IGT and NIDDM. Obesity, physical inactivity and high-fat diet have been found to predict IGT and NIDDM. Therefore, a diet and exercise intervention from diagnosis of NIDDM could improve the treatment outcome and prognosis of patients with NIDDM. Furthermore, because subjects with IGT are at increased risk for diabetes and atherosclerotic vascular disease, it is reasonable to assume that in terms of reducing the incidence and longterm consequences of NIDDM an intervention at this phase is more effective than in overt diabetes. Although the nonpharmacological approach is generally accepted as the first-line treatment of NIDDM its efficacy has often been questioned. Therefore, it is important to carry out long-term controlled studies to find out to what extent lifestyle modification could improve the metabolic control and level of major cardiovascular risk factors known to be associated with poor outcome in NIDDM. This kind of study also gave relevant experience in planning studies aiming at primary prevention of NIDDM. One-year dietary and exercise intervention on newly diagnosed NIDDM patients in Kuopio, Finland resulted in a better metabolic control and a moderate reduction in cardiovascular risk factors as compared to the conventional treatment group. After the second year of follow-up only 12.5% in the intervention group were receiving oral antidiabetic drugs vs. 34.8% in the conventional treatment group. Weight reduction and a reduced use of saturated fats appeared to be the main determinants of successful treatment results. Good aerobic capacity was associated with an increase in HDL cholesterol. A multicentre primary prevention study on IGT patients is continuing in Finland applying the same principles of intervention as used in the study on newly diagnosed NIDDM patients. Pilot results show that glucose tolerance can be improved by lifestyle changes. Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes.
                The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results.
                The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care.
                The study enrolled 2 205 patients with previously diagnosed type 2 diabetes.
                The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer.
                Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year.
                Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available.
                The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention. Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti-inflammatory drug (NSAID) use have been reported individually, but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case-control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smoking, coffee, and NSAID consumption. Odds ratios were calculated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two-way and three-way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations. With respect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR = 0.13, 95% CI = 0.06-0.29). Whether this finding reflects true biologic protection needs to be investigated.
                2007 Movement Disorder Society Lifestyle modification helps in the primary prevention of diabetes in multiethnic American, Finnish and Chinese populations. In a prospective community-based study, we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger, leaner and more insulin resistant than the above populations.
                We randomised 531 (421 men 110 women) subjects with IGT (mean age 45.9+/-5.7 years, BMI 25.8+/-3.5 kg/m(2)) into four groups. Group 1 was the control, Group 2 was given advice on lifestyle modification (LSM), Group 3 was treated with metformin (MET) and Group 4 was given LSM plus MET. The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria.
                The median follow-up period was 30 months, and the 3-year cumulative incidences of diabetes were 55.0%, 39.3%, 40.5% and 39.5% in Groups 1-4, respectively. The relative risk reduction was 28.5% with LSM (95% CI 20.5-37.3, p=0.018), 26.4% with MET (95% CI 19.1-35.1, p=0.029) and 28.2% with LSM + MET (95% CI 20.3-37.0, p=0.022), as compared with the control group. The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM, 6.9 for MET and 6.5 for LSM + MET.
                Progression of IGT to diabetes is high in native Asian Indians. Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT; there was no added benefit from combining them.
While there is good evidence from observational studies of an association between various lifestyle risk factors and gout development, there is a paucity of high-quality evidence from randomised controlled trials to either support or refute the use of lifestyle modifications for improving outcomes in people with chronic gout.