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Year : 2017  |  Volume : 4  |  Issue : 1  |  Page : 0

Diabesity in the Era of the Hapo Study

Department of Obstetrics and Gynecology. Hospital General de Catalunya, Sant Cugat del Vallès, SPAIN

Date of Web Publication6-Jul-2017

Correspondence Address:
Juan Acosta Diez
Department of Obstetrics and Gynecology. Hospital General de Catalunya, Sant Cugat del Vallès, SPAIN

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Source of Support: None, Conflict of Interest: None

DOI: 10.5530/ami.ed.4.1.1

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How to cite this article:
Diez JA. Diabesity in the Era of the Hapo Study. Acta Med Int 2017;4:0

How to cite this URL:
Diez JA. Diabesity in the Era of the Hapo Study. Acta Med Int [serial online] 2017 [cited 2022 Aug 10];4:0. Available from: https://www.actamedicainternational.com/text.asp?2017/4/1/0/209832

Noncommunicable diseases (NCDs) are the cause of almost 63% of deaths worldwide. More than 90% of these deaths occur in low and middle-income countries and could have been prevented. The 66thWorld Health Assembly endorsed the WHO Global Action Plan for prevention and control of NCDs (2013-2020) focusing on cardiovascular diseases, cancer, chronic pulmonary diseases and diabetes which make the largest contribution to overall death rate having also a huge economic and social cost. The Global Plan recognizes that conditions in which people live and work and their lifestyles influence their health and quality of life.[1]

Obesity is one of the major risk factors for cardiovascular disease and diabetes and represents a global epidemic causing 2, 8 million of deaths each year. Risks of coronary heart disease (CHD), stroke and type 2 Diabetes increase proportionally with Body mass index (BMI), but it also increases the risk of cancer of the breast, endometrium, colon, kidney and gall bladder.

Type 2 diabetes results from the body's ineffective use of insulin and its largely the result of excess body weight and physical inactivity. Adults with diabetes have a 2-3 fold increased risk of heart attacks and strokes and it is also the leading cause of kidney failure. The fact that 80-90% of patients with overweight with abdominal fat distribution are type 2 diabetics and that strategies based in weight loss have demonstrated to reduce diabetes complications, led to define a new concept: “diabesity”.[2] This new term reflects clearly the relationship between overweight and obesity as the necessary causes of type 2 diabetes and hence the need to understand pathophysiology of overweight to prevent diabetes and its complications.

It is well known that high prevalence of obesity in our societies is strongly linked to sedentary lifestyle and high-fat diets. But these factors don't have the same effects in all individuals as there must be some genetic predisposition. The theory of fetal programming of diseases was first suggested by Barker in 1989 when he reported the relationship between birthweight and ischemic heart disease and impaired glucose control.[3],[4] Since then, many evidence has been published in favor of prenatal origins of adult diseases.

Environmental factors acting during pregnancy have a large-term effect in the offspring's adult life. It has been described that newborns from diabetic mothers had greater risks of overweight and diabetes than their siblings born before the same mother developed diabetes.[5] To determine the role of the intrauterine diabetic environment per se, the prevalence of diabetes and the mean BMI was compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born before and one after the mother was diagnosed with type 2 diabetes were selected. BMI of men whose mothers had diabetes mellitus during their pregnancy was greater than in their brothers born before their mother was diagnosed with diabetes. Furthermore, this epigenetic influence can affect not only to first generation but also to grandchildren as it was described in the Dutch Hunger cohort where offspring from mothers who were pregnant during a severe famine developed increased adiposity and transmitted this phenotype to their progeny.[7]

Animal models have shown that both paternal and maternal metabolic history can produce epigenetic changes in offspringthrough different patterns of methylation of DNA, chromatin remodeling and noncoding RNA that promote gene silencing.[8]

Epigenetic changes contribute to modulate phenotype through adipose tissue programming. Adipose tissue is an active endocrine organ[9],[10] that regulates lipid synthesis, modulates insulin sensitivity but also intervenes in inflammatory response via the production of soluble factors known as adipocytokines (metaflammation).[11],[12] In obesity, this proinflammatory state provokes an imbalance between adipokines that cause insulin resistance (TNF-alpha and leptin) and those promoting insulin sensitivity like adiponectin.[13]Hyperinsulinemia resulting from insulin resistance increases lipogenesis, hepatic production of very low density lipoprotein (VLDL) and hypertriglyceridaemia.[14]

Gestational diabetes mellitus (GDM), a state of insulin resistance during pregnancy, is estimated to occur in one of every six pregnancies.[15] As with maternal obesity, this condition is in rise and the age of onset of diabetes is declining. GDM is associated with large weight at birth, shoulder dystocia, increased cesarean section rates, preeclampsia and subsequent development of type 2 diabetes. But the most important sequelae for the fetus result from long exposure to hyperglycemia and altered metabolic environment causing epigenetic changes leading to increased risk of obesity, diabetes and dyslipidemia in adult life.

Despite the great impact that gestational diabetes has on perpetuation of global diabesity problem, in most of the countries diagnosis and management has not correctly been established. Different strategies are used worldwide such as testing only risk patients, scoring systems or universal twostepped or one step approaches, every of them based on different algorithms and cut-off values.

In 2010 The International Association of Diabetes in Pregnancy Study Groups (IADPSG), after carrying out a huge international multicentric study involving 25000 patients known as the HAPO (The Hyperglycemia and Adverse Pregnancy Outcomes) study, proposed consensus cut-off values for fasting, 1 hour and 2 hour 75-OGTT, defining GDM based on odds ratio of 1.75 compared with the mean. HAPO remarked the idea of hyperglycemia as a continuous variable directly associated with adverse maternal and perinatal events. Diagnosis of GDM proposed by IADPSG is therefore more easy (one step approach) and efficient as it puts the focus on adverse events (large weight at birth, cesarean section, fetal insulin levels and neonatal fat content).

The HAPO criteria have been adopted by the WHO and the American Diabetes Association (ADA). The International Federation of Gynecology and Obstetrics (FIGO) has created a Working Group on Hyperglycemia in Pregnancy to implement evidence-based guidelines and develop projects of research and training on diagnosis and management of GDM. FIGO recommends that international attention should be focused on the link between maternal health and NCDs on the sustainable developmental goals agenda. All pregnant women should be tested using a one-step procedure following the IADPSG criteria for diagnosis of GDM. FIGO also insists that women with GDM should receive practical education on nutrition and physical exercise. If lifestyle changes are not sufficient to achieve an optimal control, then some drugs like metformin, glyburide or insulin should be considered as a safe and effective treatment. In the postpartum period a regular follow-up should be established in order to reduce maternal and child risks.

In conclusion, diabesity is a global epidemic that threatens quality of life of a growing number of people from all over the world. Epigenetic changes transmit metabolic disorders from actual to next generations, increasing seriously their risks of cardiovascular disease and diabetes. More research is needed to fully understand the link between intrauterine environment and changes in adult phenotype. Governments, institutions and health providers should launch efficient projects to raise awareness about the risks of diabesity. It's imperative to implement IADPSG recommendations and to focus on giving women adequate recommendations on nutrition and physical activity in orderto reduce the impact of GDM on noncommunicable diseases.

  References Top

Gebreyohannis T, Shibeshi W, Asres K, et al. Follow-up to the Political Declaration of the High-level Meeting of the General Assembly on the Prevention and Control of Non-communicable Diseases The. UN New York. 2013;5(1):37-44. doi:10.1007/ BF03038934.   Back to cited text no. 1
Astrup A, Finer N. Redefining Type 2 diabetes: "Diabesity" or "Obesity Dependent Diabetes Mellitus"?. Obes Rev. 2000;1(2):57- 9. doi:10.1046/j.1467-789x.2000.00013.x.   Back to cited text no. 2
Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet (London, England). 1989;2(8663):577-80. Available at: http:// www.ncbi.nlm.nih.gov/pubmed/2570282. Accessed November 13, 2016.   Back to cited text no. 3
Hales CN, Barker DJ, Clark PM, et al. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991;303(6809):1019- 22. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1954451. Accessed November 13, 2016.   Back to cited text no. 4
Dabelea D, Hanson RL, Lindsay RS, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000;49(12):2208-11. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11118027. Accessed November 13, 2016.   Back to cited text no. 5
Lawlor DA, Lichtenstein P, Langstrom N. Association of Maternal Diabetes Mellitus in Pregnancy With Offspring Adiposity Into Early Adulthood: Sibling Study in a Prospective Cohort of 280 866 Men From 248 293 Families. Circulation. 2011;123(3):258-265. doi:10.1161/CIRCULATIONAHA.110.980169.   Back to cited text no. 6
Kahn HS, Graff M, Stein AD, Lumey LH. A fingerprint marker from early gestation associated with diabetes in middle age: The Dutch Hunger Winter Families Study. Int J Epidemiol. 2009;38(1):101-9. doi:10.1093/ije/dyn158.   Back to cited text no. 7
Patti M-E. Intergenerational programming of metabolic disease: evidence from human populations and experimental animal models. Cell Mol Life Sci. 2013;70(9):1597-608. doi:10.1007/ s00018-013-1298-0.   Back to cited text no. 8
Catalano PM, Hoegh M, Minium J, et al. Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism. Diabetologia. 2006;49(7):1677-1685. doi:10.1007/ s00125-006-0264-x.   Back to cited text no. 9
Montague CT, O'Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes. 2000;49(6).   Back to cited text no. 10
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-7. doi:10.1038/nature05485.   Back to cited text no. 11
Mazaki-Tovi S, Romero R, Vaisbuch E, et al. Dysregulation of maternal serum adiponectin in preterm labor. J Matern Fetal Neonatal Med. 2009;22(10):887-904. doi:10.1080/14767050902994655.  Back to cited text no. 12
Desai M, Beall M, Ross MG. Developmental origins of obesity: Programmed adipogenesis. Curr Diab Rep. 2013;13(1):27-33. doi:10.1007/s11892-012-0344-x.   Back to cited text no. 13
Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26(2):19-39. Available at: http://www.ncbi.nlm.nih.gov/ pubmed/16278749. Accessed November 13, 2016.   Back to cited text no. 14
Hod M, Kapur A, Sacks DA, et al. The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet. 2015:S173-211. doi:10.1016/ S0020-7292(15)30007-2.  Back to cited text no. 15

  Authors Top

Juan Acosta Díez: He is a Gynecologist with special training in Prenatal Diagnosis, Obstetric Care and Endoscopic sur­gery. . After his graduation in Medicine in 1998 in the University of Salamanca ( including a year stage in Nantes) he obtained his Diploma in Obstetrics and Gynecology in 2003 from Sant Joan De Déu Hospital in Barcelona. He served in various Hospitals focusing in Prenatal diagnosis and Emergencies. In 2008 he joined General Hospital Of Catalunya where he is currently working as Senior Gynecologist and is involved in coordination of academical activities of his Department. He regularely publishes a blog of medical divulgation for patients. He has presented communications and papers in local and international conferences mainly in Perinatal Medicine and Intrapartum care. Currently involved in various Research projects.


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