Influence of maternal obesity on insulin sensitivity and secretion in offspring

Geltrude Mingrone, Melania Manco, Maria Elena Valera Mora, Caterina Guidone, Amerigo Iaconelli, Donatella Gniuli, Laura Leccesi, Chiara Chiellini, Giovanni Ghirlanda, Geltrude Mingrone, Melania Manco, Maria Elena Valera Mora, Caterina Guidone, Amerigo Iaconelli, Donatella Gniuli, Laura Leccesi, Chiara Chiellini, Giovanni Ghirlanda

Abstract

Objective: The purpose of this study was to clarify the effects of maternal obesity on insulin sensitivity and secretion in offspring.

Research design and methods: Fifty-one offspring of both sexes of obese (Ob group) and 15 offspring of normal-weight (control group) mothers were studied. Plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT). Insulin sensitivity was calculated using the oral glucose insulin sensitivity index, and insulin secretion and beta-cell glucose sensitivity were computed by a mathematical model. Fasting leptin and adiponectin were also measured. Body composition was assessed by dual-X-ray absorptiometry.

Results: No birth weight statistical difference was observed in the two groups. Of the Ob group, 69% were obese and 19% were overweight. The Ob group were more insulin resistant than the control group (398.58 +/- 79.32 vs. 513.81 +/- 70.70 ml(-1) x min(-1) x m(-2) in women, P < 0.0001; 416.42 +/- 76.17 vs. 484.242 +/- 45.76 ml(-1) x min(-1) x m(-2) in men, P < 0.05). Insulin secretion after OGTT was higher in Ob group than in control group men (63.94 +/- 21.20 vs. 35.71 +/- 10.02 nmol x m(-2), P < 0.01) but did not differ significantly in women. beta-Cell glucose sensitivity was not statistically different between groups. A multivariate analysis of variance showed that maternal obesity and offspring sex concurred together with BMI and beta-cell glucose sensitivity to determine the differences in insulin sensitivity and secretion observed in offspring.

Conclusions: Obese mothers can give birth to normal birth weight babies who later develop obesity and insulin resistance. The maternal genetic/epigenetic transmission shows a clear sexual dimorphism, with male offspring having a higher value of insulin sensitivity (although not statistically significant) associated with significantly higher insulin secretion than female offspring.

References

    1. American Diabetes Association: Type 2 diabetes in children and adolescents (Consensus Statement). Diabetes Care 23:381–389, 2000
    1. Rosenbloom AL, Joe JR, Young RS, Winter WE: Emerging epidemic of type 2 diabetes in youth. Diabetes Care 22:345–354, 1999
    1. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE: The body-mass index of twins who have been reared apart. N Engl J Med 322:1483–1487, 1990
    1. Maes HH, Neale MC, Eaves LJ: Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 27:325–351, 1997
    1. Shankar K, Harrell A, Liu X, Gilchrist JM, Ronis MJ, Badger TM: Maternal obesity at conception programs obesity in the offspring. Am J Physiol Regul Integr Comp Physiol 294:R528–R538, 2008
    1. Danielzik S, Langnase K, Mast M, Spethmann C, Muller MJ: Impact of parental BMI on the manifestation of overweight 5–7 year old children. Eur J Nutr 41:132–138, 2002
    1. Wu Q, Suzuki M: Parental obesity and overweight affect the body-fat accumulation in the offspring: the possible effect of a high-fat diet through epigenetic inheritance. Obes Rev 7:201–208, 2006
    1. Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA: Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics 111:e221–e226, 2003
    1. Khan IY, Taylor PD, Dekou V, Seed PT, Lakasing L, Graham D, Dominiczak AF, Hanson MA, Poston L: Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension 41:168–175, 2003
    1. Khan IY, Dekou V, Douglas G, Jensen R, Hanson MA, Poston L, Taylor PD: A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol 288:R127–R133, 2005
    1. Khan I, Dekou V, Hanson M, Poston L, Taylor P: Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring. Circulation 110:1097–1102, 2004
    1. Lazarin MA, Bennini JR, Pereira CL, Astiarraga BD, Ferrannini E, Muscelli E: Normal insulin sensitivity in lean offspring of obese parents. Obes Res 12:621–626, 2004
    1. Rodriguez BL, Fujimoto WY, Mayer-Davis EJ, Imperatore G, Williams DE, Bell RA, Wadwa RP, Palla SL, Liu LL, Kershnar A, Daniels SR, Linder B: Prevalence of cardiovascular disease risk factors in U.S. children and adolescents with diabetes: the SEARCH for diabetes in youth study. Diabetes Care 29:1891–1896, 2006
    1. Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ: A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548, 2001
    1. Mari A, Tura A, Gastaldelli A, Ferrannini E: Assessing insulin secretion by modeling in multiple-meal tests: role of potentiation. Diabetes 51:S221–S226, 2002
    1. Mari A, Schmitz O, Gastaldelli A, Oestergaard T, Nyholm B, Ferrannini E: Meal and oral glucose tests for the assessment of β-cell function: modeling analysis in normal subjects. Am J Physiol Endocrinol Metab 283:E1159–E1166, 2002
    1. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, Defronzo RA: β-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab 90:493–500, 2005
    1. Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD: Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab 279:E83–E87, 2000
    1. Guo F, Jen KL: High-fat feeding during pregnancy and lactation affects offspring metabolism in rats. Physiol Behav 57:681–686, 1995
    1. Bourc'his D, Bestor TH: Origins of extreme sexual dimorphism in genomic imprinting. Cytogenet Genome Res 113:36–40, 2006
    1. Thamotharan M, Garg M, Oak S, Rogers LM, Pan G, Sangiorgi F, Lee PW, Devaskar SU: Transgenerational inheritance of the insulin-resistant phenotype in embryo-transferred intrauterine growth-restricted adult female rat offspring. Am J Physiol Endocrinol Metab 292:E1270–E1279, 2007
    1. Kaminsky Z, Wang SC, Petronis A: Complex disease, gender and epigenetics. Ann Med 38:530–544, 2006
    1. Eriksson JG, Forsen TJ, Osmond C, Barker DJP: Pathways of infant and childhood growth that lead to type 2 diabetes. Diabetes Care 26:3006–3010, 2003
    1. Wei JN, Sung FC, Li CY, Chang CH, Lin RS, Lin CC, Chiang CC, Chuang LM: Low birth weight and high birth weight infants are both at an increased risk to have type 2 diabetes among schoolchildren in Taiwan. Diabetes Care 26:343–348, 2003
    1. Ong KK, Petry CJ, Emmett PM, Sandhu MS, Kiess W, Hales CN, Ness AR, Dunger DB, ALSPAC Study Team: Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels. Diabetologia 47:1064–1070, 2004

Source: PubMed

3
Abonner