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04. lomo 5-2011:lomo 3/09

Nutr Hosp. 2011;26(6):1242-1249
ISSN 0212-1611 • CODEN NUHOEQ
S.V.R. 318
Revisión
Effect of weight loss on metabolic control in people with type 2 diabetes
mellitus: systematic review
M.ª de las Cruces Souto-Gallardo1, M. Bacardí Gascón2,3 and A. Jiménez Cruz2,3
1 Estudiante del doctorado en Ciencias de la Salud. Profesor de Facultad de Ciencias de la Salud de Ensenada. UABC.
2Profesor de la Facultad de Medicina y Psicología. Universidad Autónoma de Baja California. 3Miembro del CuerpoAcadémico Consolidado de Nutrición. Postgrado en Nutrición. Tijuana. Baja California. México.
Abstract
EFECTO DE LA PÉRDIDA DE PESO
EN EL CONTROL METABÓLICO DE PERSONAS
Objective: The aim of this systematic review was to
CON DIABETES MELLITUS TIPO 2:
examine randomized clinical trials (RCT) regarding
REVISIÓN SISTEMÁTICA
long-term effects of weight loss (WL) on biological mark-
ers in people with type 2 diabetes mellitus (T2DM).

Methods: We searched for articles published in English
and Spanish recorded in the databases of Pubmed and
Objetivo: El propósito de esta revisión sistemática es
Cochrane , and the journal collections platforms of Ebsco
evaluar ensayos clínicos aleatorios (ECA) acerca de los
and Scielo between January 1, 2000 and January 1, 2010.
efectos a largo plazo de la pérdida de peso en los marcado-
Inclusion criteria included RCT with follow-up 12
res biológicos en personas con diabetes mellitus tipo 2
Results: A total of 842 articles were identified, 95 of
Métodos: Se buscaron estudios publicados en Inglés o
them contained information on the effect of WL on bio-
Español registrados en la base de datos de Pubmed y
logical markers. Twenty studies fulfilled the inclusion cri-
Cochrane, y en las plataformas de acceso a colecciones de
teria. WL percentage ranged from 0.8 to 20%. A reduc-
revistas Scielo y EBSCO, del 1° de Enero de 2000 al 1° de
tion of A1C was observed in nine studies, blood glucose in
Enero de 2010. Los criterios de inclusión fueron ECA con
seven, of total cholesterol and LDL in four, systolic and
un seguimiento a 12 meses.
diastolic blood pressure in three, and the use of hypo-
Resultados: Se identificó un total de 842 artículos, de
glycemic drugs in four; an increase of HDL was observed
los cuales 95 trataban del efecto de la pérdida de peso en
in seven studies. Remission of T2DM was reported in only
los marcadores biológicos. Veinte estudios cumplieron
one study, which included surgical treatment. The quality
con todos los criterios de inclusión. La pérdida de peso
of the studies ranged from very low to high; however, the
osciló entre 0,8 y 20%. Se observó una reducción de la
study with the longest follow-up that did not involve sur-
A1C en nueve estudios, de glucosa sanguínea en siete,
gical treatment, was 52 months.
colesterol total y LDL en cuatro, presión arterial sistólica
Conclusion: The evidence of the beneficial effect of WL
y diastólica en tres y el uso de medicamentos hipogluce-
on biological markers on long-term studies in people with
miantes en cuatro; y un incremento en los niveles de HDL
T2DM is inconclusive. These results warrant longer and
en siete estudios. La remisión de la DM2 se reportó única-
better designed studies.
mente en un estudio y era de tratamiento quirúrgico. La
calidad de los estudios osciló de muy bajo a alto; sin

embargo el estudio con mayor seguimiento que no era de
DOI:10.3305/nh.2011.26.6.5244
tratamiento quirúrgico fue de 52 meses.
Conclusión: La evidencia de que la pérdida de peso
Key words: Weight loss. Diabetes. Systematic review. tiene un efecto benéfico en los marcadores biológicos en
personas con DM2 a largo plazo no es concluyente. Estos
resultados muestran la necesidad de más estudios bien
diseñados y a largo plazo.

DOI:10.3305/nh.2011.26.6.5244
Palabras clave: Pérdida de peso. Diabetes. Revisión siste- Correspondence: Arturo Jiménez Cruz.
Calzada Universidad no. 14418.
Parque Industrial Internacional.
CP 22390 Tijuana B. C. México.
E-mail: ajimenez@uabc.edu.mx
Recibido: 17-II-2011.
1.ª Revisión: 9-III-2011.
Aceptado: 14-III-2011.
Introduction
AND “weight loss” AND “body weight changes”).
The MesH descriptors were used to search in A worldwide increase in overweight (OW) and Pubmed, Cochrane and Ebsco, and their equivalent in obesity (OB) has taken place in the past two decades, which has become a public health problem.1,2 Genetic, Inclusion criteria were the following: randomized environmental, biochemical, neurological, physio- clinical trials (RCT), papers written in English, con- logical, cultural, and socio-economic factors play ducted on T2DM people, with at least 12 months of fol- important roles in the development of OB.3,4 Along low-up, which recorded weight changes (BMI or kg), with the rise of OB, there is an important increase in metabolic parameters (A1C, blood glucose, total cho- the incidence of type 2 diabetes (T2DM).2,3 The World lesterol, LDL, HDL, Triglycerides, SBP, DBP) and the Health Organization (WHO) reports that more than use of hypoglycemic drugs (Figure 1). From the initial 220 million people worldwide have diabetes and that search, several studies were removed due to the inclu- in 2005 an estimated 1.1 million people died from dia- sion of people without diagnoses of T2DM (747), lack betes, an estimation that will be doubled by 2030.5 It of BMI or weight data (7) and those with a follow-up has been estimated that up to 75% of the risk of T2DM is attributable to OB.6 Eighty-six percent of Given the heterogeneity in study design, a meta- people with T2DM are OW or OB, and 52% are analysis was not appropriate; however, we conducted a obese.7 People with OW or OB are at a higher risk of systematic review of the available studies. Each study developing T2DM; on the other hand weight loss has was evaluated according to the number of subjects, age been associated to a decrease in risk.8-14 Several (median), percentage of retention, type of intervention, weight reduction strategies have been used to duration of intervention or follow-up (months), initial improve the metabolic control of diabetes, including and final BMI, percentage of weight change and effects lifestyle interventions,10-12 drugs,15-18 and surgical treat- ment19,20 which have shown to be effective as a pri- The quality of the randomized clinical trials was mary prevention and/or as a strategy to delay the assessed using the GRADE scale.31,32 The design of the onset of T2DM. The benefits of weight reduction in study, methodological strengths and weakness, and sig- people with T2DM are not thoroughly documented.
nificance of the findings were used to characterize the Weight lost has resulted in the reduction of use of quality of the evidence of any given study. According to hypoglycemic drugs21-24 and/or remission of dia- this scale, randomized clinical trials could receive the betes.25 In the review conducted by Aucott (2008), the number four as a maximum score. One point was sub- influences of weight loss on long-term diabetes out- tracted when the following occurred: a) significant base- comes were assessed.3 The author concluded that line differences between intervention groups (weight, intentional weight loss reduces the risk of T2DM by BMI, age, prevalence of OW or OB), b) percentage of lifestyle interventions, drugs or surgical treatment, retention ≤ 70%, c) no intention- to -treat analysis, d) including in some cases remission of the disease. This uncertainty of directness (questionable validity of instru- study also showed that in order to obtain significant ments/techniques), e) sparse data, f) high probability of reductions on blood glucose, greater and sustained reporting bias (sample, population characteristics), g) weight loss is required. Although literature reviews internal inconsistency (data, values). Two points were and meta-analyses were included in this study, the subtracted when the study showed: a) very serious results included people with and without T2DM and design limitations (sample, population characteristics), most of the studies were cohorts. Few randomized b) serious uncertainty of directness (validity of instru- clinical trials were evaluated and most of them had ments). One point was added when: a) the study pos- less than 12 months of follow-up.26-28 Since diabetes is sessed strong association without plausible confounders, a chronic disease and its implications on other health consistent, and direct evidence, b) all plausible con- problems are discovered in the long-term, the conduc- founders would have diminished the effect size. Each tion of longer follow-up studies is warranted29-30. study was assessed independently with the criteria rec- The present paper examines the long-term effects ommended by GRADE and mentioned above, by two of (≥ 12 months) of randomized clinical trials (RCT) of the authors (MSG, AJC). When there was no consis- weight loss intervention on people with diabetes.
tency a consensus was reached with the aid of a thirdauthor (MBG) using the same criteria for evaluation inquality of the studies. The search was conducted in the databases of Pubmed and Cochrane, and the journal collectionplatforms of Ebsco and Scielo. The studies were Our search resulted in 842 articles; 95 of them con- searched using the following Mesh descriptors: tained information on the effect of weight loss in meta- (“2000/01/01”: “2010/06/01”) AND (“Diabetes Mel- bolic parameters in people with T2DM (fig. 1). Twenty litus, Type 2” AND “obesity” AND “overweight” published studies (table I) fulfilled the inclusion crite- ↓ A1C and systolic BP in both Rimonabant groups There was a significant difference in weight loss between groups and hypoglycemic drug use in Orlistat group There was a significant difference in weight loss between groups There wass a significant difference in weight loss between groups ↑ systolic and diastolic BP in Sibutramine (15 mg/day) group There was a significant difference in weight loss between groups There was a significant difference in weight loss between groups There was a significant difference in weight loss between groups There was a significant difference in weight loss between groups 76% and 15% of surgical and conventional program Randomized clinical trials on the effect of weight loss in people with type 2 diabetes M.ª de las Cruces Souto-Gallardo et al.
↓ of diastolic BP in high- protein diet ↓ of hypoglycemic drugs in meal replacement group ↓ A1C, BG, diastolic BP, insulin concentration and At 18 months there was a significant difference in weight loss between groups, but not difference was found in A1C ↓ BG and systolic BP in portion-controlled diet Low-GI group had much lower likelihood of switching to a new drug or increasing dosage of hypoglycemic drugs e; F = female; MED = Mediterranean style; NA = not available; BG = blood glucose; A1C = ; TC = total cholesterol; LDL = low den rt and Education; GI = glycemic index; ADA = American Diabetes Association; ITT = Intention-to-treat.
Randomized clinical trials on the effect of weight loss in people with type 2 diabetes N = number of subjects; RET % = retention percentage; BMI = body mass index; WC = weight change; T2D = type 2 diabetes; M = mal tein; HDL = high density lipoprotein; BP = blood pressure; MUFA = monounsaturated fat; CHO = carbohydrate; DSE = Diabetes Suppo Abstracts Reviewed from ElectronicDatabases (RCT from 2000-2010): Fig. 1.—Flow diagram of the articleselection in the systematic review ofliterature. ria.22-25,33-48 A summary description of all 20 studies follow-up of this study was up to 12 months.24 Esposito included in this systematic review is presented in et al., using a Mediterranean (MED) diet, reported a table I. The mean age of study participants was 55.6 weight loss of 4.4% of BW after 48 months of follow- years (20 to 82 years). Seven studies (35%) included up,41 and Barnard et al. reported weight loss after 18 participants with insulin therapy,22,25,34-37,40,44 and four- teen studies (70%) used isocaloric diets in all partici-pants.22-24,33,34,36-38,41-43,46-48 Compliance to diets was evalua -ted by food records22,34-36,40-42,48 and diet recalls,22,34,44 while compliance to medications was evaluated by pillcount.22,33,43,45 No specific guidelines regarding physical All studies included in this revision assessed the activity (PA) modifications were provided in 45% of reduction of A1C, but only nine of them (45%) these studies.23,24,35,37-39,42,43,45 Only one study (5%) estab- reported a significant reduction after the follow-up lished a specific PA program,34 three studies (20%) period. Of these studies, five were RCT with good assessed PA levels using diary records,41,44,48 and one quality and had the maximum punctuation using the with pedometers;36 six (30%) studies generally encour- GRADE scale, four of them used drug therapy,22,23,33,47 aged participants to increase PA.22,25,33,40,46,47 and one used the MED-diet.41 One of them42 had zeropoints using the GRADE scale due to importantmethodological weaknesses such as differences between groups in baseline characteristics, insufficientsamples, retention percentage < 70%, and a lack of All studies included in this revision reported weight intention-to-treat analysis. The rest of the studies also loss after the follow-up period. According to the weight reduction strategies, a greater mean reduction was BG was assessed in only 16 studies (80%), seven of reported using surgical treatment (-20% of body which (44%) reported a significant reduction. Four of weight (BW)), followed by drug therapy (-2.3-7.7% of the studies were evaluated and received four points BW), and lifestyle interventions (-0.8-4.6% of BW).
using the GRADE scale, three of them used drug thera - Greater mean weight reduction was reported using soy- py22,33,47 and one MED-diet.41 The rest had insufficient based meal replacements (-4.6% of BW); however, the M.ª de las Cruces Souto-Gallardo et al.
studies had a follow-up of 12 months, four studies hada follow up ≥12 months, and the longest non surgical The effect of weight loss on lipid values was study had a follow-up of 48 months. One of the studies assessed in 18 studies (90%). Four of them (20%) with the longest follow-up (24 months) reported reported a significant reduction in total cholesterol, weight loss, reduction in BG, A1C, and the use of three of them used Orlistat to reduce body weight22,33,42 hypoglycemic drugs after bariatric surgery, however, and received four points using the GRADE scale; one the sample size was insufficient to obtain 80% of statis- study44 used the low-GI diet or ADA-diet but had tical power, and no intention-to -treat analysis was important methodological weaknesses. Also, four of used, which resulted in an evaluation score of 2. One of them (20%) reported significant reduction in LDL, two the studies with the follow-up of 18 months reported used Orlistat (4 points with GRADE scale),22,23 one the reductions in weight; however, the quality score of this low-GI diet (0 points with GRADE scale)44 and one the study was 2 because neither intention-to-treat nor sta- MED-diet (4 points with GRADE scale).41 Seven studies tistical power was reported. One of the longest studies (35%) reported an elevation of HDL, three using (18 months) had the highest quality score (4) and drugs,33,42,47 one with a portion controlled diet,38 one reported no significant changes in any parameter. The with the MED-diet,41 one with the high-MUFA and study that included low carbohydrate Mediterranean diet also had the highest quality score and reported areduction of BG, A1C and LDL and an increase ofHDL, after 48 months of follow-up, with no difference Previous reviews assessed the impact of weight loss Sixteen studies (80%) assessed blood pressure, of in patients with T2DM, but the results included people which only three (19%) reported a significant reduc- with and without T2DM; they only assessed one type tion in systolic BP23,38,47 and three others in diastolic of intervention, and most of the studies were cohorts.
BP.36,37,43 In one study using sibutramine (15 mg/day) a Few RCT were evaluated and most of them had a fol- significant elevation of systolic, diastolic BP and pulse low-up of less than 12 months.3,18,49,50 This study includes RCT with a follow-up ≥ 12 months in order toassess the long term sustainability of the effects on bio-logical markers. The results observed in this study con- firm that the metabolic control of people with diabetesis challenging at the long-term. Nine studies (45%) assessed if there was a reduction People with OW or OB have an increased risk of in the use of hypoglycemic drugs. A significant reduc- developing T2DM, and weight loss has been associ- tion was observed in four (44%) of these studies. Two ated with a reduced risk.8-14 Several large RCT have used Orlistat,22,23 one used surgical treatment,25 and one shown that weight loss might be an important manage- ment strategy for OW and OB persons with pre-dia-betes, as it may delay or prevent the progression of cli -nically defined T2DM.10,51 Consistently, some studies have shown that weight loss in obese people withT2DM can significantly improve glycemic control, and Remission of T2DM was only reported in the study some subjects can discontinue insulin or oral therapy.49 using surgical treatment as the weight control strategy.25 However, most studies assessed short-term improve- The remission was observed in the surgical group ments and long-term effects were less described.
(76%) and in the conventional treatment group (15%).
The results of this study suggests that the treatment of OB and OW on people with T2DM should focus inencouraging lifestyle changes and improving biologi- Discussion
cal markers, instead of establishing weight loss goalsthat are difficult to reach, as an intermediate objective This revision indicates that the effect of WL on bio- to improve biological markers. However, these results logical markers on long-term studies in people with warrant longer and better designed studies.
T2DM is inconclusive. WL percentage ranged from The strength of this study is the inclusion of studies 0.8 to 20%, reduction in A1C was observed in nine out of ≥ 12 months of follow-up, since diabetes is a chronic of 20 studies, blood glucose in seven out of 16, total disease and its implications on other health problems cholesterol and LDL in four out of 18, systolic and are discovered in the long-term; therefore, the result are diastolic blood pressure in three out of 16 and the use of not overestimated by shorter-term intervention (< 6 hypoglycemic drugs in four out of nine; an increase of months). Unfortunately, several studies had to be HDL was observed in seven out of 18 studies. In addi- excluded due to the inclusion of combined data from tion, remission of T2DM was only reported in the study people with and without diabetes. The main limitation in which subjects underwent bariatric surgery. Most of the study is the lack of a meta-analysis due to the het- erogeneity of the studies’ design. In addition, the treat- Study: a randomized study of Orlistat as an adjunct to lifestyle ment strategy was mixed, ranging from diet manage- changes for the prevention of type 2 diabetes in obese patients.
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Microsoft word - q110earnings_pr_04_21_10.doc

For Immediate Release Genzyme Reports Financial Results for the First Quarter of 2010 -------------------------- Provides Update on Product Supply and Consent Decree Terms CAMBRIDGE, Mass. – Genzyme Corp. (NASDAQ: GENZ) today reported that first-quarter revenue was $1.07 billion, compared with $1.15 billion in the same period last year, reflecting limited shipments of Cer

Thermotolerance generated by plant/fungal symbiosis

ble S2) than those of nonsymbiotic plants insoils Յ40°C. In soils above 40°C, nonsymbi-otic plants did not survive while symbioticplants thrived. The beneficial effect of fungalsymbiosis increased with soil temperatures,demonstrating that Curvularia sp. providedthermal protection for D. lanuginosum . We rei-Regina S. Redman,1,2 Kathy B. Sheehan,3,5 Richard G. Stout,4,5solated Curvula

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