Transcript PowerPoint - 埼玉医科大学総合医療センター 内分泌・糖尿病内科

Journal Club
Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A,
Gudbjörnsdottir S, Wedel H, Clements M, Dahlqvist S, Lind M.
Excess Mortality among Persons with Type 2 Diabetes.
N Engl J Med. 2015 Oct 29;373(18):1720-32. doi: 10.1056/NEJMoa1504347.
Inge TH, Courcoulas AP, Jenkins TM, Michalsky MP, Helmrath MA, Brandt
ML, Harmon CM, Zeller MH, Chen MK, Xanthakos SA, Horlick M, Buncher
CR; Teen-LABS Consortium.
Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents.
N Engl J Med. 2015 Nov 6. [Epub ahead of print]
2015年11月12日 8:30-8:55
８階 医局
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
Matsuda, Masafumi
the ERFC Coordinating Centre at the Department of Public
Health and Primary Care, University of Cambridge
N Engl J Med 2011;364:829-41.
N Engl J Med 2011;364:829-41.
N Engl J Med 2011;364:829-41.
N Engl J Med 2011;364:829-41.
N Engl J Med 2014; 371:1972-1982
From the Department of Molecular and Clinical Medicine, University of
Gothenburg (M.T., A.R., S.G., M.L.), Center of Registers in Region Västra
Götaland (A.-M.S.), Statistiska Konsultgruppen (A.P.), and Nordic School of
Public Health (H.W.), Gothenburg, and the Department of Medicine, NU Hospital
Group, Trollhättan and Uddevalla (M.T., S.D., M.L.) — all in Sweden; Saint Luke’s
Mid America Heart Institute (M.K.) and Children’s Mercy Hospital (M.C.),
University of Missouri–Kansas City School of Medicine, Kansas City; and the
University of Kansas School of Medicine, Kansas City (M.C.).
N Engl J Med 2015; 373:1720-1732October 29, 2015DOI: 10.1056/NEJMoa1504347
Background
The excess risks of death from any cause and
death from cardiovascular causes among
persons with type 2 diabetes and various levels of
glycemic control and renal complications are
unknown. In this registry-based study, we
assessed these risks according to glycemic
control and renal complications among persons
with type 2 diabetes.
Methods
We included patients with type 2 diabetes who
were registered in the Swedish National Diabetes
Register on or after January 1, 1998. For each
patient, five controls were randomly selected from
the general population and matched according to
age, sex, and county. All the participants were
followed until December 31, 2011, in the Swedish
Registry for Cause-Specific Mortality.
* Plus–minus values are means ±SD.
Educational level was categorized as low
(compulsory only), intermediate, or high
(university level or similar). Percentages
for the glycated hemoglobin level were
based on values from the National
Glycohemoglobin Standardization
Program, and concentrations were
based on values from the International
Federation of Clinical Chemistry. The
body-mass index is the weight in
kilograms divided by the square of the
height in meters.
† The following codes from the
International Classification of Diseases,
10th Revision, were used: I21 for acute
myocardial infarction; I20 through I25 for
coronary heart disease; I48 for atrial
fibrillation; I50 for heart failure; I61, I62.9,
I63, I64, and I67.9 for stroke; and C00
through C97 for cancer.
The following ICD-9 and ICD-10 codes were collected: coronary
heart disease: ICD-9 410-414, and ICD-10 I20-I25 (including
acute myocardial infarction: ICD-9 410, and ICD-10 I21); stroke:
ICD-9 431, 432X, 433, 434, 436, 437X, and ICD10 I61, I62.9, I63,
I64, I67.9; hospitalization for heart failure ICD-9 428, and ICD-10
I50; atrial fibrillation ICD-9 427D, and ICD-10 I48; and cancer ICD9 140-208, and ICD-10 C00-C97. Cardiovascular mortality was
defined as ICD-10 I00-I99, death from cancer as ICD-10 C00-C97,
diabetes-related death as ICD-10 E10-E14, external death (e.g.
due to accident, exposure to fire, smoke, flames, or forces of
nature, intentional self-harm, etc.) as ICD-10 V00-Y99, and all
other causes of death other than those listed. For renal dialysis
and transplantation, the following codes were used: ICD-9 V42A,
V45B, V56A, V56W, and ICD-10 Z94.0, Z49, Z99.2.
Figure 1. Adjusted Hazard Ratios
for Death from Any Cause and
Death from Cardiovascular
Causes, According to Year
Range and Age Category, in
Models 2 and 3.
The analysis, which was based on
Cox regression, was adjusted for
time-updated age and sex and was
stratified according to duration of
diabetes in the diabetes group (0 to
1 years, >1 to 5 years, >5 to 10
years, >10 to 20 years, or >20
years) in model 2; controls were
assigned to the same stratification
category as the patients in the
diabetes group with whom they
were matched.
In model 3, the analysis was
additionally adjusted for country of
birth (Sweden or other), educational
level (low [compulsory only],
intermediate, or high [university
level or similar]), and status with
respect to history of coexisting
conditions at baseline.
Results
The mean follow-up was 4.6 years in the diabetes group and 4.8 years in
the control group. Overall, 77,117 of 435,369 patients with diabetes (17.7%)
died, as compared with 306,097 of 2,117,483 controls (14.5%) (adjusted
hazard ratio, 1.15; 95% confidence interval [CI], 1.14 to 1.16). The rate of
cardiovascular death was 7.9% among patients versus 6.1% among
controls (adjusted hazard ratio, 1.14; 95% CI, 1.13 to 1.15). The excess
risks of death from any cause and cardiovascular death increased with
younger age, worse glycemic control, and greater severity of renal
complications. As compared with controls, the hazard ratio for death from
any cause among patients younger than 55 years of age who had a
glycated hemoglobin level of 6.9% or less (≤52 mmol per mole of
nonglycated hemoglobin) was 1.92 (95% CI, 1.75 to 2.11); the
corresponding hazard ratio among patients 75 years of age or older was
0.95 (95% CI, 0.94 to 0.96). Among patients with normoalbuminuria, the
hazard ratio for death among those younger than 55 years of age with a
glycated hemoglobin level of 6.9% or less, as compared with controls, was
1.60 (95% CI, 1.40 to 1.82); the corresponding hazard ratio among patients
75 years of age or older was 0.76 (95% CI, 0.75 to 0.78), and patients 65 to
74 years of age also had a significantly lower risk of death (hazard ratio,
0.87; 95% CI, 0.84 to 0.91).
Conclusions
Mortality among persons with type 2 diabetes, as
compared with that in the general population,
varied greatly, from substantial excess risks in
large patient groups to lower risks of death
depending on age, glycemic control, and renal
complications.
(Funded by the Swedish government and others.)
Message
スウェーデンで2型糖尿病患者43万5369人と一般
集団から年齢、性別などでマッチさせた対照211
万7483人を対象に、糖尿病患者の過剰死亡リス
クを登録ベースの研究で調査。糖尿病患者の対
照に対する調整後ハザード比は全死因死亡1.15
（95％ CI, 1.14 - 1.16）、心血管死1.14
（95％ CI, 1.13 - 1.15）だった。年齢、血糖
コントロール、腎合併症の重症度別にみるとリ
スクが低いグループもあった。
http://www.m3.com/clinical/journal/15965
SLEEVE
BYPASS
Biliopancreatic diversion
Adjustable gastric banding
Roux-en-Y gastric bypass
Sleeve gastrectomy
Vertical banded gastroplasty
with duodenal switch
A meta-analysis from University of California, Los Angeles reports the
following weight loss at 36 months
Biliopancreatic diversion - 53 kg
Roux-en-Y gastric bypass (RYGB) - 41 kg
Open - 42 kg
Laparoscopic - 38 kg
Adjustable gastric banding - 35 kg
Vertical banded gastroplasty - 32 kg
Sleeve gastrectomy ?
From the Cincinnati Children’s Hospital Medical Center (T.H.I., T.M.J., M.A.H.,
M.H.Z., S.A.X.) and the University of Cincinnati (C.R.B.), Cincinnati, and
Nationwide Children’s Hospital, Columbus (M.P.M.) — all in Ohio; the University
of Pittsburgh Medical Center, Pittsburgh (A.P.C.); Texas Children’s Hospital,
Baylor College of Medicine, Houston (M.L.B.); Women and Children’s Hospital,
University of Buffalo, Buffalo, NY (C.M.H.); University of Alabama at
Birmingham, Birmingham (M.K.C.); and the National Institute of Diabetes and
Digestive and Kidney Diseases, Bethesda, MD (M.H.).
November 6, 2015DOI: 10.1056/NEJMoa1506699
Background
Bariatric surgery is increasingly considered
for the treatment of adolescents with severe
obesity, but few prospective adolescentspecific studies examining the efficacy and
safety of weight-loss surgery are available
to support clinical decision making.
Methods
We prospectively enrolled 242 adolescents
undergoing weight-loss surgery at five U.S.
centers. Patients undergoing Roux-en-Y gastric
bypass (161 participants) or sleeve gastrectomy
(67) were included in the analysis. Changes in
body weight, coexisting conditions,
cardiometabolic risk factors, and weight-related
quality of life and postoperative complications
were evaluated through 3 years after the
procedure.
* Plus–minus values are means ±SD.
CI denotes confidence interval.
† Race and ethnic background were
self-reported.
‡ Data are for 183 participants in total
(131 participants who underwent
gastric bypass and 52 participants
who underwent sleeve gastrectomy),
with values from 7 patients (6
participants who underwent gastric
bypass and 1 participant who
underwent sleeve gastrectomy)
excluded because of pregnancy.
§Data are for 179 participants in total
(131 participants who underwent
gastric bypass and 48 participants
who underwent sleeve gastrectomy).
¶ Data are for 173 participants in total
(125 participants who underwent
gastric bypass and 48 participants
who underwent sleeve gastrectomy),
with values from 7 patients (6
participants who underwent gastric
bypass and 1 participant who
underwent sleeve gastrectomy)
excluded because of pregnancy.
Figure 1. Weight Changes and Prevalence of Dyslipidemia during the 3-Year
Period after Bariatric Surgery.
Panel A shows the modeled least-squares mean percent changes in weight from
baseline at each study visit during the 3 years after Roux-en-Y gastric bypass surgery
(bypass) or vertical sleeve gastrectomy (sleeve).
Panel B shows the modeled least-squares mean prevalences of dyslipidemia at each
study visit during the 3 years after Roux-en-Y gastric bypass surgery (bypass) or vertical
sleeve gastrectomy (sleeve). I bars in both panels represent 95% confidence intervals.
Figure S4: Graphic representation of prevalence (Y-axis) of dyslipidemia for RYGB
subjects over time (X-axis) using age appropriate or adult lipid cut-points.
APPENDIX I. Clarification of rationale for use of terms in dyslipidemia definitions
For a population that is aging out of pediatric and into adult definitions for abnormal lipid values, the resolution of dyslipidemia could
be calculated in several ways. In this analysis, we have used ageappropriate, pediatric cut-points for abnormal lipids for those who
were < age 21 and adult cutpoints for those who were 21 or older. This was a decision that was made after careful consideration of
the most appropriate strategy to arrive at an accurate interpretation of our findings for an aging study population, wherein norms for
lipid values change at 21 years of age. When we analyzed the dyslipidemia prevalence data using adult cut-points for all time points
irrespective of age of the participant, we found that the adult definition included 10% more participants at baseline (eg.,
overestimated prevalence) as shown in Figure S3 below for the gastric bypass cohort. Further exploration led us to find that it was
not as much the difference in the triglyceride or LDL cut-point, but the HDL which was responsible for the difference at baseline. For
females (the majority of this cohort), the HDL adult cut-point for abnormal is <50mg/dL while for pediatric ages, it is <40mg/dL,
meaning that use of the adult cut-point for children overestimates the prevalent dyslipidemia at baseline and to some extent at each
time point. Over time, there was a similar fall in prevalence using age appropriate cut-points for each time point vs. using adult cutpoints. Thus, while it may be “cleaner” in a sense to use adult cut-points across the board during this longitudinal analysis, it appears
to artificially elevate the prevalence of dyslipidemia and thus age appropriate cut-points were used across all time points.
* The criteria used to define each coexisting condition are provided in the Supplementary Appendix.
† Generalized mixed models were used to calculate the modeled results.
‡ The proportion of participants in remission was calculated as the number of participants (among those for whom sufficient data
were available at 3 years to determine whether the coexisting condition was present) who did not have the condition at 3 years after
the procedure, divided by the number of participants (among those for whom sufficient data were available at 3 years to define
whether the coexisting condition was present) who had had the condition at baseline.
§ The model failed because of the small sample size.
Diabetes mellitus (DM). DM at baseline was defined by study investigators taking into consideration patient selfreport of prior diagnosis, as well as prior medical records from referring physician, use of medications for DM,
baseline HbA1c of ≥6.5%, or fasting glucose of at least 126 mg/dL, or oral glucose tolerance results in prior 6
months. Participants reporting having polycystic ovarian syndrome who did not meet laboratory criteria for DM and
were not taking a DM medication other than metformin were not considered to have diabetes. Participants who were
on metformin at baseline for weight management or for insulin resistance, with no other indication of a prior
diagnosis of DM documented and no laboratory findings consistent with the diagnosis of DM were not considered to
have DM. Remission of DM was defined as no use of medication for DM, and HbA1c < 6.5%, or, if HbA1c was not
available, FBG <126mg/dL.
Specifically, the data for this variable were obtained as follows:
•
•
•
•
•
Preoperative (PO) form, question 9b;
Comorbidity Assessment-Baseline (CAB) and follow up (CAF) forms, question 6c, 6d, 7, 18;
Medical Assessment – Baseline (MAB) form, question 14;
All declared medications from the MED form;
Central lab measured baseline fasting glucose and HbA1c values
Pre-diabetes (Pre-DM). Pre-DM at baseline was defined as no use of medications for DM with HbA1c of ≥5.7% but
<6.5%, or HbA1c not available, fasting blood glucose 100 to less than 126 mg/dL. Remission of Pre-DM was
defined as HbA1c < 5.7%, or, if HbA1c was not available, FBG <100mg/dL.
Abnormal Kidney Function. The presence of abnormal kidney function was determined using accepted
criterial for chronic kidney disease (CKD)3 using glomerular filtration rate (GFR), as determined by
cystatin C levels4, where GFR=77.24 x (Cys C)-1.2623; microalbuminuria was defined as urine albumin to
creatinine ratio > 0.03; CKD stages were defined as follows:
•
•
•
•
•
•
Normal = GFR>60 and no microalbuminuria
CKD stage 1 = Microalbuminuria with GFR ≥ 90
CKD stage 2 = Microalbuminuria with GFR of 60-89
CKD Stage 3 = GFR of 30-59
CKD stage 4 = GFR of 15-29
CKD stage 5 = GFR < 15
For this study, abnormal kidney function was defined as any stage (1-5) of CKD. Resolution of abnormal
kidney function was defined as attaining a GFR>60 with no evidence of kidney injury (urine albumin to
creatinine ratio ≤ 0.03).
Elevated blood pressure. Blood pressure (BP) was measured at the time of the study visit and use of medications for
control of BP was recorded on medication use form (MED) or comorbidity assessment baseline (CAB) or follow up
(CAF) form. Due to the fact that blood pressures were measured on one, rather than multiple separate occasions, the
term hypertension is not being used, but instead, the term elevated BP is being used in this analysis. Elevated BP is
otherwise defined in a manner consistent with that used to define hypertension: use of BP medications or SBP ≥
95th P or DBP ≥ 95th P (for age, sex, height) if <18 years of age; or if ≥18 years, SBP>140 mmHg or DBP > 90
mmHg was used. Remission of elevated BP required that no medications for BP were used, and SBP and DBP were
normal for age. Specifically, the data for this variable were obtained/analyzed as previously described 2:
• Systolic and diastolic BP were measured using a Welch Allyn Spot Vital Signs monitor 4200B as previously
described. For home visits, a monitor was shipped to the field examiner.
• Measurement of BP was done with appropriately sized cuff and after the patient has been seated quietly, with
feet flat on the floor, in an erect but comfortable posture for at least five minutes, and for at least thirty minutes
since the patient has smoked or consumed caffeinecontaining beverages.
Dyslipidemia. Dyslipidemia was defined for those <21 years of age as fasting triglycerides (TG) ≥130 mg/dL, or
low density lipoprotein cholesterol (LDL-C) ≥130 mg/dL, or high density lipoprotein cholesterol (HDL-C) <
40mg/dL, or use of lipid lowering medications (LLM). Remission of dyslipidemia: If <21 years of age, at follow-up,
remission of dyslipidemia was defined as TG <130 mg/dL, and LDL-C <130 mg/dL, and HDL-C ≥40 mg/dL, and
no use of LLM. If age was ≥ 21 years, resolution of dyslipidemia was defined as TG <200 mg/dL, and LDL-C <160
mg/dL, and HDL-C ≥40 mg/dL (males) or HDL-C ≥50 mg/dL (females), and no use of LLM. Specifically, the data
for this variable were obtained as follows:
• Central laboratory measured triglyceride, LDL cholesterol, HDL cholesterol at baseline and follow-up;
• LLM assessment was derived during analysis from Comorbidity Assessment-Baseline (CAB) or follow up
(CAF) form, Question 5 – selection equals: “treatment with single medication for dyslipidemia” or “treatment
with two or more medications for dyslipidemia”;
• Medications (MED) form, subject-reported use of any antilipemic Rx.
Results
The mean (±SD) baseline age of the participants was 17±1.6 years,
and the mean body-mass index (the weight in kilograms divided by the
square of the height in meters) was 53; 75% of the participants were
female, and 72% were white. At 3 years after the procedure, the mean
weight had decreased by 27% (95% confidence interval [CI], 25 to 29) in
the total cohort, by 28% (95% CI, 25 to 30) among participants who
underwent gastric bypass, and by 26% (95% CI, 22 to 30) among those
who underwent sleeve gastrectomy. By 3 years after the procedure,
remission of type 2 diabetes occurred in 95% (95% CI, 85 to 100) of
participants who had had the condition at baseline, remission of
abnormal kidney function occurred in 86% (95% CI, 72 to 100),
remission of prediabetes in 76% (95% CI, 56 to 97), remission of
elevated blood pressure in 74% (95% CI, 64 to 84), and remission of
dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life
also improved significantly. However, at 3 years after the bariatric
procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the
participants, and 13% (95% CI, 9 to 18) of the participants had
undergone one or more additional intraabdominal procedures.
Conclusions
In this multicenter, prospective study of bariatric
surgery in adolescents, we found significant
improvements in weight, cardiometabolic health,
and weight-related quality of life at 3 years after
the procedure. Risks associated with surgery
included specific micronutrient deficiencies and
the need for additional abdominal procedures.
(Funded by the National Institute of Diabetes and
Digestive and Kidney Diseases and others; TeenLABS ClinicalTrials.gov number, NCT00474318.)
Message
青少年（少女）の減量手術！
日本でもこれはやっておいた方がよいような症
例が多いと感じる。あまり問題の起こる前に
「手術」は選択としてありうるであろう。
本人の受け止め方はどんなものであろうか？