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Semin Reprod Med 2020; 38(06): 333-341
DOI: 10.1055/s-0041-1723777
Review Article

The Double Whammy of Obesity and Diabetes on Female Reproductive Health

Eleanor P. Thong 
1   Monash Centre for Health Research and Implementation, Monash University, Melbourne, Australia
2   Department of Diabetes and Vascular Medicine, Monash Health, Melbourne, Australia
,
Christy Burden
3   Faculty of Health Sciences, University of Bristol, Bristol, United Kingdom
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Abstract

The rising global prevalence of obesity and diabetes, especially in youth, confers substantial metabolic consequences and increased mortality in affected individuals. While obesity is strongly tied to the development of insulin resistance and type 2 diabetes, emerging evidence shows that obesity rates are also increasing exponentially in those with type 1 diabetes, contributing to insulin resistance and cardiometabolic sequelae. In addition, both obesity and diabetes can exert adverse effects on female reproductive health independently, with the presence of both conditions likely to exacerbate reproductive dysfunction in this cohort. If the current trends in obesity and diabetes incidence persist, it is likely that more women will be at risk of obesity- and diabetes-related reproductive disorders. This review aims to describe the epidemiology and mechanisms of obesity in women with diabetes, and summarize current literature regarding reproductive disorders in diabetes and weight management strategies in this cohort.

Keywords

obesity - diabetes - female reproduction - polycystic ovary syndrome


Publication History

Article published online:
17 February 2021

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  • References

  • 1 Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt) 2018; 27: 444-457
    CrossrefPubMedGoogle Scholar
  • 2 Leitner DR, Frühbeck G, Yumuk V. et al. Obesity and type 2 diabetes: two diseases with a need for combined treatment strategies - EASO can lead the way. Obes Facts 2017; 10 (05) 483-492
    CrossrefPubMedGoogle Scholar
  • 3 Polsky S, Ellis SL. Obesity, insulin resistance, and type 1 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 2015; 22 (04) 277-282
    CrossrefPubMedGoogle Scholar
  • 4 Censin JC, Nowak C, Cooper N, Bergsten P, Todd JA, Fall T. Childhood adiposity and risk of type 1 diabetes: a Mendelian randomization study. PLoS Med 2017; 14 (08) e1002362
    CrossrefPubMedGoogle Scholar
  • 5 Wilkin TJ. The accelerator hypothesis: a unifying explanation for type-1 and type-2 diabetes. Nestle Nutr Workshop Ser Clin Perform Programme 2006; 11: 139-153
    CrossrefPubMedGoogle Scholar
  • 6 Frühbeck G, Toplak H, Woodward E, Yumuk V, Maislos M, Oppert JM. Executive Committee of the European Association for the Study of Obesity. Obesity: the gateway to ill health - an EASO position statement on a rising public health, clinical and scientific challenge in Europe. Obes Facts 2013; 6 (02) 117-120
    CrossrefPubMedGoogle Scholar
  • 7 Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes 2008; 32: 1431-1437
    CrossrefPubMedGoogle Scholar
  • 8 Kramer H, Cao G, Dugas L, Luke A, Cooper R, Durazo-Arvizu R. Increasing BMI and waist circumference and prevalence of obesity among adults with type 2 diabetes: the National Health and Nutrition Examination Surveys. J Diabetes Complications 2010; 24 (06) 368-374
    CrossrefPubMedGoogle Scholar
  • 9 Leibson CL, Williamson DF, Melton III LJ. et al. Temporal trends in BMI among adults with diabetes. Diabetes Care 2001; 24 (09) 1584-1589
    CrossrefPubMedGoogle Scholar
  • 10 Pulgaron ER, Delamater AM. Obesity and type 2 diabetes in children: epidemiology and treatment. Curr Diab Rep 2014; 14 (08) 508
    CrossrefPubMedGoogle Scholar
  • 11 Kaufman FR, Shaw J. Type 2 diabetes in youth: rates, antecedents, treatment, problems and prevention. Pediatr Diabetes 2007; 8 (Suppl. 09) 4-6
    CrossrefPubMedGoogle Scholar
  • 12 American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000; 23 (03) 381-389
    CrossrefPubMedGoogle Scholar
  • 13 Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996; 128 (5, Pt 1): 608-615
    CrossrefPubMedGoogle Scholar
  • 14 Haines L, Wan KC, Lynn R, Barrett TG, Shield JP. Rising incidence of type 2 diabetes in children in the U.K. Diabetes Care 2007; 30 (05) 1097-1101
    CrossrefPubMedGoogle Scholar
  • 15 Liu LL, Lawrence JM, Davis C. et al; SEARCH for Diabetes in Youth Study Group. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth study. Pediatr Diabetes 2010; 11 (01) 4-11
    CrossrefPubMedGoogle Scholar
  • 16 DuBose SN, Hermann JM, Tamborlane WV. et al. Obesity in youth with type 1 diabetes in Germany, Austria, and the United States. J Pediatr 2015; 167: 627-632
    CrossrefPubMedGoogle Scholar
  • 17 Conway B, Miller RG, Costacou T. et al. Temporal patterns in overweight and obesity in type 1 diabetes. Diabet Med 2010; 27 (04) 398-404
    CrossrefPubMedGoogle Scholar
  • 18 Dahlström EH, Sandholm N, Forsblom CM. et al. Body mass index and mortality in individuals with type 1 diabetes. J Clin Endocrinol Metab 2019; 104 (11) 5195-5204
    CrossrefPubMedGoogle Scholar
  • 19 Thong EP, Milat F, Joham AE, Mishra GD, Teede H. Obesity, menstrual irregularity and polycystic ovary syndrome in young women with type 1 diabetes: a population-based study. Clin Endocrinol (Oxf) 2020; 93 (05) 564-571
    CrossrefPubMedGoogle Scholar
  • 20 Meldrum DR, Morris MA, Gambone JC. Obesity pandemic: causes, consequences, and solutions-but do we have the will?. Fertil Steril 2017; 107 (04) 833-839
    CrossrefPubMedGoogle Scholar
  • 21 McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med 2010; 363 (24) 2339-2350
    CrossrefPubMedGoogle Scholar
  • 22 Goodarzi MO. Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol 2018; 6 (03) 223-236
    CrossrefPubMedGoogle Scholar
  • 23 Luczyński W, Fendler W, Ramatowska A. et al. Polymorphism of the FTO gene influences body weight in children with type 1 diabetes without severe obesity. Int J Endocrinol 2014; 2014: 630712
    CrossrefPubMedGoogle Scholar
  • 24 Łuczyński W, Głowińska-Olszewska B, Bossowski A. The influence of clinical and genetic factors on the development of obesity in children with type 1 diabetes. Diabetes Metab Res Rev 2016; 32 (07) 666-671
    CrossrefPubMedGoogle Scholar
  • 25 Corbin KD, Driscoll KA, Pratley RE, Smith SR, Maahs DM, Mayer-Davis EJ. Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON). Obesity in type 1 diabetes: pathophysiology, clinical impact, and mechanisms. Endocr Rev 2018; 39 (05) 629-663
    CrossrefPubMedGoogle Scholar
  • 26 Fernandez-Twinn DS, Hjort L, Novakovic B, Ozanne SE, Saffery R. Intrauterine programming of obesity and type 2 diabetes. Diabetologia 2019; 62 (10) 1789-1801
    CrossrefPubMedGoogle Scholar
  • 27 Lindell N, Carlsson A, Josefsson A, Samuelsson U. Maternal obesity as a risk factor for early childhood type 1 diabetes: a nationwide, prospective, population-based case-control study. Diabetologia 2018; 61 (01) 130-137
    CrossrefPubMedGoogle Scholar
  • 28 Chen X, Devaraj S. Gut microbiome in obesity, metabolic syndrome, and diabetes. Curr Diab Rep 2018; 18 (12) 129
    CrossrefPubMedGoogle Scholar
  • 29 Marlow AL, Rowe CW, Anderson D. et al. Young children, adolescent girls and women with type 1 diabetes are more overweight and obese than reference populations, and this is associated with increased cardiovascular risk factors. Diabet Med 2019; 36 (11) 1487-1493
    CrossrefPubMedGoogle Scholar
  • 30 Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the Diabetes Control and Complications Trial. Diabetes Care 2001; 24 (10) 1711-1721
    CrossrefPubMedGoogle Scholar
  • 31 Thong EP, Codner E, Laven JSE, Teede H. Diabetes: a metabolic and reproductive disorder in women. Lancet Diabetes Endocrinol 2020; 8 (02) 134-149
    CrossrefPubMedGoogle Scholar
  • 32 Holman RR, Thorne KI, Farmer AJ. et al; 4-T Study Group. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 2007; 357 (17) 1716-1730
    CrossrefPubMedGoogle Scholar
  • 33 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352 (9131): 837-853
    CrossrefPubMedGoogle Scholar
  • 34 Balkau B, Home PD, Vincent M, Marre M, Freemantle N. Factors associated with weight gain in people with type 2 diabetes starting on insulin. Diabetes Care 2014; 37 (08) 2108-2113
    CrossrefPubMedGoogle Scholar
  • 35 Riddell MC, Gallen IW, Smart CE. et al. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol 2017; 5 (05) 377-390
    CrossrefPubMedGoogle Scholar
  • 36 Colberg SR, Sigal RJ, Fernhall B. et al; American College of Sports Medicine, American Diabetes Association. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care 2010; 33 (12) e147-e167
    CrossrefPubMedGoogle Scholar
  • 37 Nolan RC, Raynor AJ, Berry NM, May EJ. Self-reported physical activity using the International Physical Activity Questionnaire (IPAQ) in Australian adults with type 2 diabetes, with and without peripheral neuropathy. Can J Diabetes 2016; 40 (06) 576-579
    CrossrefPubMedGoogle Scholar
  • 38 Driscoll KA, Corbin KD, Maahs DM. et al; Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON). Biopsychosocial aspects of weight management in type 1 diabetes: a review and next steps. Curr Diab Rep 2017; 17 (08) 58
    CrossrefPubMedGoogle Scholar
  • 39 Liu XM, Liu YJ, Zhan J, He QQ. Overweight, obesity and risk of all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus: a dose-response meta-analysis of prospective cohort studies. Eur J Epidemiol 2015; 30 (01) 35-45
    CrossrefPubMedGoogle Scholar
  • 40 Saydah SH, Imperatore G, Beckles GL. Socioeconomic status and mortality: contribution of health care access and psychological distress among U.S. adults with diagnosed diabetes. Diabetes Care 2013; 36 (01) 49-55
    CrossrefPubMedGoogle Scholar
  • 41 Goldsammler M, Merhi Z, Buyuk E. Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis. Reprod Biol Endocrinol 2018; 16 (01) 45
    CrossrefPubMedGoogle Scholar
  • 42 Wise LA, Rothman KJ, Mikkelsen EM, Sørensen HT, Riis A, Hatch EE. An internet-based prospective study of body size and time-to-pregnancy. Hum Reprod 2010; 25 (01) 253-264
    CrossrefPubMedGoogle Scholar
  • 43 Bellver J, Rossal LP, Bosch E. et al. Obesity and the risk of spontaneous abortion after oocyte donation. Fertil Steril 2003; 79 (05) 1136-1140
    CrossrefPubMedGoogle Scholar
  • 44 He Y, Tian J, Oddy WH, Dwyer T, Venn AJ. Association of childhood obesity with female infertility in adulthood: a 25-year follow-up study. Fertil Steril 2018; 110 (04) 596-604.e1
    CrossrefPubMedGoogle Scholar
  • 45 Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online 2011; 23 (04) 421-439
    CrossrefPubMedGoogle Scholar
  • 46 Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol 2015; 29 (04) 498-506
    CrossrefPubMedGoogle Scholar
  • 47 Boots C, Stephenson MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med 2011; 29 (06) 507-513
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. SART Writing Group. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod 2011; 26 (01) 245-252
    CrossrefPubMedGoogle Scholar
  • 49 Broughton DE, Moley KH. Obesity and female infertility: potential mediators of obesity's impact. Fertil Steril 2017; 107 (04) 840-847
    CrossrefPubMedGoogle Scholar
  • 50 Brannian JD, Hansen KA. Leptin and ovarian folliculogenesis: implications for ovulation induction and ART outcomes. Semin Reprod Med 2002; 20 (02) 103-112
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010; 8: 41
    CrossrefPubMedGoogle Scholar
  • 52 Álvarez-Blasco F, Botella-Carretero JI, San Millán JL, Escobar-Morreale HF. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med 2006; 166 (19) 2081-2086
    CrossrefPubMedGoogle Scholar
  • 53 Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93 (01) 162-168
    CrossrefPubMedGoogle Scholar
  • 54 Bizzarri C, Benevento D, Ravà L. et al. Ovarian hyperandrogenism in adolescents and young women with type I diabetes is primarily related to birth weight and body mass index. Fertil Steril 2011; 96 (06) 1497-1502.e1
    CrossrefPubMedGoogle Scholar
  • 55 Naderpoor N, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ. Obesity and polycystic ovary syndrome. Minerva Endocrinol 2015; 40 (01) 37-51
    PubMedGoogle Scholar
  • 56 Sim SY, Chin SL, Tan JL, Brown SJ, Cussons AJ, Stuckey BG. Polycystic ovary syndrome in type 2 diabetes: does it predict a more severe phenotype?. Fertil Steril 2016; 106 (05) 1258-1263
    CrossrefPubMedGoogle Scholar
  • 57 Snider AP, Wood JR. Obesity induces ovarian inflammation and reduces oocyte quality. Reproduction 2019; 158 (03) R79-R90
    CrossrefPubMedGoogle Scholar
  • 58 Jonasson JM, Brismar K, Sparén P. et al. Fertility in women with type 1 diabetes: a population-based cohort study in Sweden. Diabetes Care 2007; 30 (09) 2271-2276
    CrossrefPubMedGoogle Scholar
  • 59 National Diabetes Audit Programme. National Pregnancy in Diabetes Audit Report: England, Wales and the Isle of Man. London, UK: NHS Digital; 2018
    Google Scholar
  • 60 Schweiger BM, Snell-Bergeon JK, Roman R, McFann K, Klingensmith GJ. Menarche delay and menstrual irregularities persist in adolescents with type 1 diabetes. Reprod Biol Endocrinol 2011; 9: 61
    CrossrefPubMedGoogle Scholar
  • 61 Schroeder B, Hertweck SP, Sanfilippo JS, Foster MB. Correlation between glycemic control and menstruation in diabetic adolescents. J Reprod Med 2000; 45 (01) 1-5
    PubMedGoogle Scholar
  • 62 Barata DS, Adan LF, Netto EM, Ramalho AC. The effect of the menstrual cycle on glucose control in women with type 1 diabetes evaluated using a continuous glucose monitoring system. Diabetes Care 2013; 36 (05) e70
    CrossrefPubMedGoogle Scholar
  • 63 Kelsey MM, Braffett BH, Geffner ME. et al; TODAY Study Group. Menstrual dysfunction in girls from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. J Clin Endocrinol Metab 2018; 103 (06) 2309-2318
    CrossrefPubMedGoogle Scholar
  • 64 Dorman JS, Steenkiste AR, Foley TP. et al; Familial Autoimmune and Diabetes (FAD) Study. Menopause in type 1 diabetic women: is it premature?. Diabetes 2001; 50 (08) 1857-1862
    CrossrefPubMedGoogle Scholar
  • 65 Whitworth KW, Baird DD, Stene LC, Skjaerven R, Longnecker MP. Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother and Child Cohort Study. Diabetologia 2011; 54 (03) 516-522
    CrossrefPubMedGoogle Scholar
  • 66 Wiebe JC, Santana A, Medina-Rodríguez N. et al; T1DGC. Fertility is reduced in women and in men with type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium (T1DGC). Diabetologia 2014; 57 (12) 2501-2504
    CrossrefPubMedGoogle Scholar
  • 67 Isik S, Ozcan HN, Ozuguz U. et al. Evaluation of ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with type 2 diabetes mellitus. J Clin Endocrinol Metab 2012; 97 (01) 261-269
    CrossrefPubMedGoogle Scholar
  • 68 Persson M, Cnattingius S, Wikström AK, Johansson S. Maternal overweight and obesity and risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. Diabetologia 2016; 59 (10) 2099-2105
    CrossrefPubMedGoogle Scholar
  • 69 Balsells M, García-Patterson A, Gich I, Corcoy R. Maternal and fetal outcome in women with type 2 versus type 1 diabetes mellitus: a systematic review and metaanalysis. J Clin Endocrinol Metab 2009; 94 (11) 4284-4291
    CrossrefPubMedGoogle Scholar
  • 70 Grams J, Garvey WT. Weight loss and the prevention and treatment of type 2 diabetes using lifestyle therapy, pharmacotherapy, and bariatric surgery: mechanisms of action. Curr Obes Rep 2015; 4 (02) 287-302
    CrossrefPubMedGoogle Scholar
  • 71 Mottalib A, Kasetty M, Mar JY, Elseaidy T, Ashrafzadeh S, Hamdy O. Weight management in patients with type 1 diabetes and obesity. Curr Diab Rep 2017; 17 (10) 92
    CrossrefPubMedGoogle Scholar
  • 72 Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes--causes, effects and coping strategies. Diabetes Obes Metab 2007; 9 (06) 799-812
    CrossrefPubMedGoogle Scholar
  • 73 Valla V. Therapeutics of diabetes mellitus: focus on insulin analogues and insulin pumps. Exp Diabetes Res 2010; 2010: 178372
    CrossrefPubMedGoogle Scholar
  • 74 Bush MA. Intensive diabetes therapy and body weight: focus on insulin detemir. Endocrinol Metab Clin North Am 2007; 36 (Suppl. 01) 33-44
    CrossrefPubMedGoogle Scholar
  • 75 Schechter R, Reutrakul S. Management of severe insulin resistance in patients with type 1 diabetes. Curr Diab Rep 2015; 15 (10) 77
    CrossrefPubMedGoogle Scholar
  • 76 Burchardt P, Zawada A, Tabaczewski P. et al. Metformin added to intensive insulin therapy reduces plasma levels of glycated but not oxidized low‑density lipoprotein in young patients with type 1 diabetes and obesity in comparison with insulin alone: a pilot study. Pol Arch Med Wewn 2013; 123 (10) 526-532
    PubMedGoogle Scholar
  • 77 Dejgaard TF, Frandsen CS, Holst JJ, Madsbad S. Liraglutide for treating type 1 diabetes. Expert Opin Biol Ther 2016; 16 (04) 579-590
    CrossrefPubMedGoogle Scholar
  • 78 Wang W, Liu H, Xiao S, Liu S, Li X, Yu P. Effects of insulin plus glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating type 1 diabetes mellitus: a systematic review and meta-analysis. Diabetes Ther 2017; 8 (04) 727-738
    CrossrefPubMedGoogle Scholar
  • 79 Herrmann K, Brunell SC, Li Y, Zhou M, Maggs DG. Impact of disease duration on the effects of pramlintide in type 1 diabetes: a post hoc analysis of three clinical trials. Adv Ther 2016; 33 (05) 848-861
    CrossrefPubMedGoogle Scholar
  • 80 Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 2016; 134 (10) 752-772
    CrossrefPubMedGoogle Scholar
  • 81 Lee PC, Ganguly S, Goh SY. Weight loss associated with sodium-glucose cotransporter-2 inhibition: a review of evidence and underlying mechanisms. Obes Rev 2018; 19 (12) 1630-1641
    CrossrefPubMedGoogle Scholar
  • 82 Koliaki C, Liatis S, le Roux CW, Kokkinos A. The role of bariatric surgery to treat diabetes: current challenges and perspectives. BMC Endocr Disord 2017; 17 (01) 50
    CrossrefPubMedGoogle Scholar
  • 83 Buchwald H, Estok R, Fahrbach K. et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009; 122 (03) 248-256.e5
    CrossrefPubMedGoogle Scholar
  • 84 Schauer PR, Burguera B, Ikramuddin S. et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg 2003; 238 (04) 467-484 , discussion 84–85
    CrossrefPubMedGoogle Scholar
  • 85 Landau Z, Kowen-Sandbank G, Jakubowicz D. et al. Bariatric surgery in patients with type 1 diabetes: special considerations are warranted. Ther Adv Endocrinol Metab 2019; 10: 2042018818822207
    CrossrefPubMedGoogle Scholar
  • 86 Faucher P, Poitou C, Carette C. et al. Bariatric surgery in obese patients with type 1 diabetes: effects on weight loss and metabolic control. Obes Surg 2016; 26 (10) 2370-2378
    CrossrefPubMedGoogle Scholar