PracticeUpdate: Endocrinology

OBESITY

14

Glycaemic index values are unsuitable for guidance of food choices Comment by Marion Franz, MS, RD, CDE

JOURNAL SCAN Smoking cessation is associated with risk of obesity and diabetes Obesity Take-home message • The authors of this review evaluated the effect of smoking cessation on body weight and diabetes. • Smoking cessation is often associated with weight gain, obesity, and diabetes; however, interventions aimed at both smoking cessation and weight control may improve outcomes. Abstract OBJECTIVE Most smokers gain weight after quitting, and some develop new onset obesity and type 2 diabetes. The purpose of this paper is to synthesize the current science investigating the consequences of tobacco cessation on body weight and diabetes, as well as interven- tion strategies that minimize or prevent weight gain while still allowing for successful tobacco cessation. METHODS Systematic reviews and relevant studies that were published since prior reviews were selected. RESULTS Smoking cessation can cause excessive weight gain in some individuals and can be associated with clinically significant outcomes such as diabetes or obesity onset. Interventions that combine smoking cessation and weight control can be effective for improving cessation andminimizingweight gain but need to be tested in specific populations. CONCLUSIONS Despite the health benefits of quitting tobacco, post- cessation weight gain and new onset obesity and diabetes are a sig- nificant concern. Promising interventions may need to be more widely applied to reduce the consequences of both obesity and tobacco use. The effect of tobacco cessation on weight gain, obesity, and diabetes risk. Obesity 2016;24:1834-1841, Bush T, Lovejoy JC, Deprey M, Carpenter KM RESULTS Themean ± SDGI value for white bread was 62 ± 15 when calculated by using the recommended method. Mean intra- and interindividual CVs were 20% and 25%, respectively. Increasing sample size, replication of reference and test foods, and length of blood sampling, as well as AUC calculation method, did not improve the CVs. Among the biological factors assessed, insulin index and glycated hemoglobin values explained 15% and 16% of the variability in mean GI value for white bread, respectively. CONCLUSIONS These data indicate that there is substantial variability in individual responses to GI value determinations, demonstrating that it is unlikely to be a good approach to guiding food choices. Additionally, even in healthy individuals, glycemic status significantly contributes to the variability in GI value estimates. Am J Clin Nutr 2016 Sep 07;[Epub ahead of print], Matthan NR, Ausman LM, Meng H, et al. Estimating the reliability of glycemic index values and potential sources of methodological and biological variability The American Journal of Clinical Nutrition Take-home message • This study investigated use of the glycemic index (GI) of a food for dietary guidance, and the results show an in- consistency in the mean intra- and inter-individual CVs for white bread (20% and 25%, respectively). Changes made to methodological variables showed no improvement to the CVs, and evaluation of biological factors revealed that a portion of the variability in mean GI value for white bread was explained by the insulin index and glycated hemoglobin. • It seems that the GI of a food varies significantly by gly- cemic status of the patient. The variability in individual responses to GI indicates that this marker is questionable for guiding food choices. Abstract BACKGROUND The utility of glycemic index (GI) values for chronic disease risk management remains controversial. Although ab- solute GI value determinations for individual foods have been shown to vary significantly in individuals with diabetes, there is a dearth of data on the reliability of GI value determinations and potential sources of variability among healthy adults. OBJECTIVE We examined the intra- and inter-individual vari- ability in glycemic response to a single food challenge and methodologic and biological factors that potentially mediate this response. DESIGN The GI value for white bread was determined by using standardized methodology in 63 volunteers free from chronic disease and recruited to differ by sex, age (18–85 y), and body mass index [BMI (in kg/m 2 ): 20–35]. Volunteers randomly under- went 3 sets of food challenges involving glucose (reference) and white bread (test food), both providing 50 g available car- bohydrates. Serum glucose and insulin were monitored for 5 h postingestion, and GI values were calculated by using different area under the curve (AUC) methods. Biochemical variables were measured by using standard assays and body composition by dual-energy X-ray absorptiometry.

I n an attempt to better determine why discrepancies as to the value of implementing low glycaemic index (GI) diets exist, this very well conducted study determined the intra-individ- ual and inter-individual variability in glycaemic response to a single food challenge and possible methodological and biological factors that affect responses among healthy adults (n = 63). 1 Subjects consumed either 50 g available glucose from a 500  mL glucose drink or 96.25 g white bread in three sets of random order food challenges (5-h study period) and the incremental area under the blood glucose response curve (AUC) and insulin response were measured. The intra-individual CV was 20% and the inter-individual CV was 25%, ranging from 2% to 77%. The authors concluded that the high degree of glucose variability (GV) demonstrates the difficulty in classifying foods into the 3 commonly used GI categories (low, medium, and high), thus invalidating the practical applicability of the GI value. Due to the substantial variability in individual responses to GI value results, the GI is unlikely to be a helpful approach to guide food choices.

GV is also an issue in persons with diabetes, and this study provides a better understanding of outcomes from systematic reviews of the usefulness of the GI concept for these individuals. TheAmerican DiabetesAssociation systematic review concluded, “In general, there is little difference in glycaemic control and CVD risk factors between low-GI and high GI or other diets.” 2 The Academy of Nutrition and Dietetics Evidence Analysis Library reviewed 5 studies meeting predetermined criteria (12-weeks or longer studies, 10 or more subjects per study arm, and 80% com- pletion rate) and concluded, “Studies regarding the relationship of GI, independent of weight loss, reported no significant effect on HbA1c in adults with type 2 diabetes. No studies were identified in adults with type 1 diabetes.” 3 A previous Cochrane review by 2 Australian researchers reported benefit of the GI concept for persons with diabetes. 4 However, a year-long study conducted in subjects with type 2 diabetes that reporting no differences in glycaemic control from a low versus a high-GI diet was excluded (based on an unusual exclusion criteria – subjects could not be in optimal control of their diabetes) and was based primarily on older, smaller, and shorter duration studies. Therefore, the substantial variability in individual responses in “healthy” and diabetic patients results in the inability to distinguish between glycaemic response between foods, thus invalidating the practical applicability of the GI value. References 1. Matthan NR, Ausman LM, Meng H, et al. Am J Clin Nutr doi: 10.3945/ ajcn.116.137208 (first published ahead of print September 7, 2016) 2. Wheeler ML, Dunbar SA, Jaacks LM, et al. Diabetes Care 2012;35:434-445. 3. Academy of Nutrition and Dietetics Diabetes Type 1 and 2 Systematic Review and Guideline, 2015. Academy of Nutrition and Dietetics Evidence Analysis Library: www.andeal.org/topic.cfm?menus=5305 4. Thomas D, Elliott EJ. Cochrane Database Syst Rev 2009 Jan;(1):CD006296. doi: 10. 1002/14651858.CD006296.pub2. Ms Franz is a nutrition/health consultant with Nutrition Concepts by Franz, Inc. She co-edited the 2012 American Diabetes Association Nutrition Therapy for Diabetes, is the lead author on the Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guidelines

for Type 1 and Type 2 Diabetes, authored American Diabetes Association nutrition position statements and technical reviews, and was editor of the American Association of Diabetes Educators Core Curriculum for Diabetes Education, 4th and 5th editions.

JOURNAL SCAN Metformin beneficial for overweight due to antipsychotics in children with autism JAMA Psychiatry Take-home message

who received at least 1 dose of medication. RESULTS Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Met- formin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs pla- cebo, -0.10 [95% CI, -0.16 to -0.04]; P=.003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4.04 to -1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five partici- pants in the metformin group discontinued treatment owing to adverse events (agita- tion, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastroin- testinal adverse events during a significantly higher percentage of treatment days (25.1% vs 6.8%; P=.005). CONCLUSIONS AND RELEVANCE Metformin may be effective in decreasing weight gain asso- ciated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD. Metformin for treatment of overweight induced by atypical antipsychotic medication in young people with autism spectrum disorder: a randomized clinical trial. JAMA Psychiatry 2016;73:928-937, Anagnostou E, Aman MG, Handen BL, et al

• The authors of this double-blind, randomized controlled trial evaluated the effective- ness of metformin compared with placebo for the treatment of weight gain due to atypical antipsychotics in children and adolescents with autism spectrum disorder (ASD). Compared with the placebo group, the metformin group had significantly greater reductions in BMI and body weight at 16 weeks. There was no difference in metabolic variables at 16 weeks. • In children and adolescents with ASD and weight gain due to antipsychotics, metformin may be effective for weight reduction. Abstract

4 centers in Toronto, Ontario, Canada; Co- lumbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015. INTERVENTIONS Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years. MAIN OUTCOMES AND MEASURES The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent- to-treat sample comprising all participants

IMPORTANCE Atypical antipsychotic medi- cations are indicated for the treatment of irritability and agitation symptoms in chil- dren with autism spectrum disorder (ASD). Unfortunately, these medications are as- sociated with weight gain and metabolic complications that are especially troubling in children and with long-term use. OBJECTIVE To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in chil- dren and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. DESIGN, SETTING, AND PARTICIPANTS A 16- week, double-blind, placebo-controlled, randomized clinical trial was conducted at

PRACTICEUPDATE ENDOCRINOLOGY