Journal Club

1. Journal Club Cahill LE, Chiuve SE, Mekary RA, Jensen MK, Flint AJ, Hu FB, Rimm EB. Prospective Study of Breakfast Eating and Incident Coronary Heart Disease in a Cohort of Male US Health Professionals. Circulation. 2013 Jul 23;128(4):337-43. Goldfine AB, Fonseca V, Jablonski KA, Chen YD, Tipton L, Staten MA, Shoelson SE; Targeting Inflammation Using Salsalate in Type 2 Diabetes Study Team*. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2013 Jul 2;159(1):1-12. 埼玉医科大学　総合医療センター　内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田　昌文 Matsuds, Masafumi 2013年8月8日8:30-8:55 ８階　医局

2. the Departments of Nutrition (L.E.C., S.E.C., R.A.M., M.K.J., A.J.F., F.B.H., E.B.R.) and Epidemiology (F.B.H., E.B.R.), Harvard School of Public Health, Boston, MA; and Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (F.B.H., E.B.R.), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA. Circulation. 2013;128:337–343.

3. Background—Among adults, skipping meals is associated with excess body weight, hypertension, insulin resistance, and elevated fasting lipid concentrations. However, it remains unknown whether specific eating habits regardless of dietary composition influence coronary heart disease (CHD) risk. The objective of this study was to prospectively examine eating habits and risk of CHD.

4. Methods—Eating habits, including breakfast eating, were assessed in 1992 in 26 902 American men 45 to 82 years of age from the Health Professionals Follow-up Study who were free of cardiovascular disease and cancer. During 16 years of follow-up, 1527 incident CHD cases were diagnosed. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for CHD, adjusted for demographic, diet, lifestyle, and other CHD risk factors.

6. BMI indicates body mass index; CHD, coronary heart disease; CI, confidence interval; and RR, relative risk. *In addition to age, this model is further adjusted for diet factors: diet quality (quintiles of alternate Healthy Eating Index 2010 score), energy intake (quintiles of kcal/d), alcohol intake (0, 0.1–<5, 5–<15, 15–<30, ≥30 g/d, missing), and eating frequency (1–8 times a day). †In addition to age and diet factors, this model is further adjusted for demographic factors: smoking (never, past, current), marital status (yes, no, missing), full-time work status (yes, no, missing), parental myocardial infarction <60 years of age (yes/no), and physical examination in last 2 years (yes/no). ‡In addition to age, diet and demographic factors, this model is further adjusted for activity factors: physical activity (quintiles of metabolic equivalent h/wk), television (asked in categories 0–1.5, 2.0–6.0, 7.0–20.0, ≥21.0 h/wk, missing), and sleep (<7, 7–8, >9 h/24 h, missing). §In addition to age, diet, demographic, and activity factors, this model is further adjusted for BMI updated every 2 years (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m2, missing). ‖In addition to age, diet, demographic, and activity factors, this model is further adjusted for diabetes mellitus (yes/no), hypertension (yes/no), and hypercholesterolemia (yes/no), updated every 2 years. Further adjustment for late-night eating, stress, antidepressant medication, daily number of cigarettes among smokers, body weight change, and specific dietary components such as folate, whole grains, fiber, or saturated fat did not substantially alter results.

7. BMI indicates body mass index; CHD, coronary heart disease; CI, confidence interval; and RR, relative risk. *In addition to age, this model is further adjusted for diet factors: diet quality (quintiles of alternate Healthy Eating Index 2010 score), energy intake (quintiles of kcal/d), alcohol intake (0, 0.1–<5, 5–<15, 15–<30, ≥30 g/d, missing), and eating frequency (1–8 times a day). †In addition to age and diet factors, this model is further adjusted for demographic factors: smoking (never, past, current), marital status (yes, no, missing), full-time work status (yes, no, missing), parental myocardial infarction <60 years of age (yes/no), and physical examination in last 2 years (yes/no). ‡In addition to age, diet and demographic factors, this model is further adjusted for activity factors: physical activity (quintiles of metabolic equivalent h/wk), television (asked in categories 0–1.5, 2.0–6.0, 7.0–20.0, ≥21.0 h/wk, missing), and sleep (<7, 7–8, >9 h/24 h, missing). §In addition to age, diet, demographic, and activity factors, this model is further adjusted for BMI updated every 2 years (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m2, missing). ‖In addition to age, diet, demographic, and activity factors, this model is further adjusted for diabetes mellitus (yes/no), hypertension (yes/no), and hypercholesterolemia (yes/no), updated every 2 years. Further adjustment for breakfast, stress, antidepressant medication, daily number of cigarettes among smokers, body weight change, and specific dietary components such as folate, whole grains, fiber, or saturated fat did not substantially alter results.

9. CI indicates confidence interval; and RR, relative risk. The model is adjusted for age, diet quality (alternate Healthy Eating Index 2010 score), energy intake, alcohol intake, smoking, marital status, full-time work status, parental myocardial infarction <60 years of age, physical examination in last 2 years, physical activity (metabolic equivalent h/wk), television (h/wk), and sleep hours (h/24 h). *There are 97 fewer cases. †The reference group is breakfast eaters. ‡The reference group is those who do not eat late at night.

10. Results—Men who skipped breakfast had a 27% higher risk of CHD compared with men who did not (relative risk, 1.27; 95% confidence interval, 1.06–1.53). Compared with men who did not eat late at night, those who ate late at night had a 55% higher CHD risk (relative risk, 1.55; 95% confidence interval, 1.05–2.29). These associations were mediated by body mass index, hypertension, hypercholesterolemia, and diabetes mellitus. No association was observed between eating frequency (times per day) and risk of CHD.

11. Conclusions—Eating breakfast was associated with significantly lower CHD risk in this cohort of male health professionals.

12. Message 一日の食事の中で朝食が一番重要とされているが、やはり朝食を抜くと健康に良くないようだ。米ハーバード大学公衆衛生学部のLeah E. Cahill氏（栄養学）らは、米国の男性医療従事者を対象とした研究（HPFS）から、朝食を食べない人では心臓病を発症するリスクが高い傾向にあると、7月23日発行の米医学誌「Circulation」（2013; 128: 337-343）に発表した。ただし、直接的な関係ではなく、肥満度や高血圧、糖尿病などが関与しているという。

14. Drs. Goldfine and Shoelson: Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. Dr. Fonseca: Tulane University Health Sciences Center, Department of Medicine, Section of Endocrinology, 1430 Tulane Avenue, SL 53, New Orleans, LA 70112. Dr. Jablonski and Ms. Tipton: The George Washington University, The Biostatistics Center, 6110 Executive Boulevard, Suite 750, Rockville, MD 20852. Dr. Chen: Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048. Dr. Staten: National Institute of Diabetes and Digestive and Kidney Diseases, Division of Diabetes, Endocrinology, and Metabolic Diseases, Building 2 DEM, Room 6107, 6707 Democracy Boulevard, Bethesda, MD 20892. Ann Intern Med. 2013;159:1-12.

15. Background: Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM). Objective: To assess 1-year efficacy and safety of salsalate in T2DM.

16. Design: Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643) Setting: 3 private practices and 18 academic centers in the United States. Patients: Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (≦225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% who were treated for diabetes. Intervention: 286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n ＝140) or salsalate, 3.5 g/d (n ＝146), in addition to current therapies, and 283 participants were analyzed (placebo, n ＝137; salsalate, n ＝146). Measurements: Change in hemoglobin A1c level (primary outcome) and safety and efficacy measures.

17. Figure 1. Study flow diagram. All data were used through trial completion or point of withdrawal for patients with a baseline HbA1c measurement. Two participants withdrew after randomization but before the blood draw; 1 additional participant did not have baseline HbA1c measurement from the laboratory. Percentages may not sum to 100 due to rounding. HbA1c = hemoglobin A1c.

18. ACE = angiotensin-converting enzyme; ARB =angiotensin-receptor blocker; BMI =body mass index; CVD =cardiovascular disease; DPP-4 =dipeptidyl peptidase-4; max =maximum; min =minimum; T1DM =type 1 diabetes mellitus; T2DM =type 2 diabetes mellitus. * All values are numbers (percentages) unless otherwise indicated. Percentages may not sum to 100 due to rounding. † Patients appearing in _1 category are grouped with “other.” ‡ A history of stroke, angina, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty. § Systolic blood pressure _140 mm Hg or diastolic blood pressure _90 mm Hg or taking antihypertensive drugs, including loop, thiazide, or potassium-sparing diuretics, potassium supplements, ACE inhibitors, ARBs, calcium-channel blockers, peripheral _-blockers, central _-adrenergic agonists, _-blockers, vasodilators, or reserpine. _ Low-density lipoprotein cholesterol level _3.89 mmol/L (_150 mg/dL) or taking cholesterol-lowering drugs, including bile acid sequestrants, 3-hydroxy-3- methylglutaryl coenzyme A reductase inhibitors (statins), fibrates, cholesterol absorption inhibitors, niacin, and nicotinic acid. ¶ First-degree relatives. ** Some participants take statins and “other” lipid medications. †† Some participants take ACE inhibitors or ARBs and “other” antihypertensive agents. ‡‡ 81–325 mg/d.

25. Results: The mean HbA1c level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, －0.53% to －0.21%; P ＜0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged.

26. Limitation: Trial duration and number of patients studied were insufficient to determine long-term risk–benefit of salsalate in T2DM. Conclusion: Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted. Primary Funding Source: National Institutes of Health.

27. Message 2型糖尿病（DM）患者283人を対象に、サリチル酸1年投与の有効性と安全性を無作為化プラセボ対照試験で検討。サリチル酸群はプラセボ群に比べ、48 週間の平均HbA1c値が0.37％低く（P＜0.001）、併用の糖尿病薬を減らしても血糖値の改善が見られた。好中球数、リンパ球数なども減少し、サリチル酸の抗炎症作用が示された。