Body weight, not insulin sensitivity or secretion, may predict spontaneous weight changes in nondiabetic and prediabetic subjects: the RISC study期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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Reference	N	Men/Women	Age (years)	BMI (kg/m²)	Follow-up (years)	Method	Result
Body weight, not insulin sensitivity or secretion, may predict spontaneous weight changes in nondiabetic and prediabetic subjects: the RISC study

Authors:	Rebelos Eleni Muscelli Elza Natali Andrea Balkau Beverley Mingrone Geltrude Piatti Piermarco Konrad Thomas Mari Andrea Ferrannini Ele;RISC Study Investigators

Institution:	Department of Internal Medicine, University of Pisa, Italy.

Abstract:	OBJECTIVE Previous studies have found that high insulin sensitivity predicts weight gain; this association has not been confirmed. Our aim was to systematically analyze metabolic predictors of spontaneous weight changes. RESEARCH DESIGN AND METHODS In 561 women and 467 men from the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort (mean age 44 years, BMI range 19–44 kg/m², 9% impaired glucose tolerance) followed up for 3 years, we measured insulin sensitivity (by a euglycemic clamp) and β-cell function (by modeling of the C-peptide response to oral glucose and by acute insulin response to intravenous glucose). RESULTS Insulin sensitivity was similar in weight gainers (top 20% of the distribution of BMI changes), weight losers (bottom 20%), and weight stable subjects across quartiles of baseline BMI. By multiple logistic or linear regression analyses controlling for center, age, sex, and baseline BMI, neither insulin sensitivity nor any β-cell function parameter showed an independent association with weight gain; this was true in normal glucose tolerance, impaired glucose tolerance, and whether subjects progressed to dysglycemia or not. Baseline BMI was significantly higher in gainers (26.1 ± 4.1 kg/m²) and losers (26.6 ± 3.7 kg/m²) than in weight stable subjects (24.8 ± 3.8 kg/m², P < 0.0001 for both gainers and losers). Baseline waist circumference (or equivalently, BMI or weight) was a positive, independent predictor of both weight gain and weight loss (odds ratio 1.48 95% CI 1.12–1.97]) in men and (1.67 1.28–2.12]) in women. In men only, better insulin sensitivity was an additional independent predictor of weight loss. CONCLUSIONS Neither insulin sensitivity nor insulin secretion predicts spontaneous weight gain. Individuals who have attained a higher weight are prone to either gaining or losing weight regardless of their glucose tolerance.The epidemic of obesity and the attendant increased risk of diabetes and cardiovascular disease pose a demand for devising and implementing strategies to combat and/or prevent obesity. Although much work has addressed the metabolic consequences of weight gain, relatively few studies have focused on the metabolic predictors of weight change. Because insulin resistance is, like obesity, a major risk factor for the development of diabetes, it is of special interest to establish the relation of insulin resistance to body weight changes. Several reports have examined the relationship between insulin action and weight gain (1) found that insulin sensitivity, not insulin resistance, predicted spontaneous weight gain. Likewise, in a small clinical study in women (5), clamp-based insulin sensitivity predicted weight regain after initial weight loss. Other studies using a variety of surrogate indices of insulin sensitivity in larger groups of individuals, however, have yielded mixed results, with roughly half of them reporting an association between insulin sensitivity and weight gain and the other half a relation of insulin resistance to subsequent weight gain. With regard to insulin secretion, again, the findings from studies using a host of proxies for β-cell function have been inconclusive (
Swinburn et al. (1991) (1)	192	104/88	18–41	33–35	3.5	Clamp	Insulin resistance is associated with a reduced risk of weight gain.
Valdez et al. (1994) (2)	1,493	634/859	25–64	24–28	8	OGTT	Insulin resistance attenuates further weight gain among the obese.
Schwartz et al. (1995) (3)	97	64/33	25	34–35	3	MTT, OGTT, IVGTT	Relatively reduced insulin release predicts weight gain.
Hoag et al. (1995) (4)	789	382/407	20–74	21–30	4.3	Fasting insulin	Higher initial fasting insulin decreases the risk of subsequent weight gain.
Yost et al. (1995) (5)	10	0/10	36 ± 2	34–36	1.5	Clamp	Change in insulin sensitivity predicts weight regain after an initial weight loss.
Hodge et al. (1996) (6)	3,156	1,486/1,670	25–74	22–26	5	HOMA-IR	In Chinese men, insulin resistance predicts weight gain; in Asian, Indian, and Creole subjects, insulin sensitivity predicts weight gain.
Sigal et al. (1997) (7)	107	48/59	33 ± 10	—	16 ± 4	IVGTT	High AIR predicts weight gain in offspring of two diabetic parents.
Odeleye et al. (1997) (8)	328	147/181	5–9	—	9 ± 2	Fasting insulin	In Pima Indian children, fasting hyperinsulinemia is associated with weight gain.
Folsom et al. (1998) (9)	11,198	4,975/6,223	45–64	21–33	7	Fasting insulin	Hyperinsulinemia predicts weight loss in ARIC but not in CARDIA.
Gould et al. (1999) (10)	767	325/442	40–65	21–30	4.4	OGTT	In middle-aged women, reduced first-phase insulin release predicts weight gain; fasting hyperinsulinemia predicts a higher waist-to-hip ratio.
Wedick et al. (2001) (11)	725	308/417	50–89	21–31	8	HOMA-IR	Insulin resistance is associated with weight loss in the elderly.
Travers et al. (2002) (12)	95	47/48	10–15	—	3	FSIVGTT	Insulin resistance during puberty predicts less subcutaneous fat accumulation.
Mayer-Davis et al. (2003) (13)	1,194	534/660	55	23–37	5	IVGTT	Measures of insulin metabolism appear to have little effect on weight change.
Mosca et al. (2004) (14)	782	349/433	20–74	20–30	14	QUICKI	Insulin resistant individuals are susceptible to weight gain.
Howard et al. (2004) (15)	3,389	0/3,389	62	27	3	HOMA-IR	In postmenopausal women, insulin resistance predicts weight gain.
Silver et al. (2006) (16)	105	64/41	28 ± 9	21–31	26 ± 4	IVGTT	Neither AIR nor insulin sensitivity predicts weight gain.
Pannacciulli et al. (2007) (17)	253	166/87	18–44	—	7 ± 4	Clamp	In Pima Indians, insulin sensitivity does not predict weight changes in multivariate analysis.
Morrison et al. (2008) (18)	639	0/639	18–19	14–35	10	HOMA-IR	Girls in the top tertiles of HOMA-IR and dietary fat had a greater 10-year increase in BMI.
Adam et al. (2009) (19)	96	67/29	Children	22–32	1	FSIVGTT	In children, a decrease in insulin sensitivity is associated with a higher fat mass gain.

Open in a separate windowMTT, meal tolerance test; FSIVGTT, frequently sampled IVGTT; QUICKI, quantitative insulin sensitivity check index.In the present work, we examined the longitudinal data of the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study, in which a large cohort of nondiabetic subjects underwent a standardized euglycemic-hyperinsulinemic clamp to measure insulin sensitivity and an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) to derive measures of β-cell function. Specifically, we asked the question whether weight changes at follow-up, in either direction, could be predicted by baseline insulin sensitivity and/or β-cell function.

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OBJECTIVE

RESEARCH DESIGN AND METHODS

RESULTS

CONCLUSIONS