Sex differences in type 2 diabetes: Focus on disease course and outcomes

Diabetes, Metabolic Syndrome and Obesity

Volumn 7, Issue , 2014, Pages 409-420

  Arnetz, Lisa ^a,b   Ekberg, Neda Rajamand ^a,b   Alvarsson, Michael ^a,b  

^a KAROLINSKA INSTITUTE   (Sweden)

^b Metabolism and Diabetes   (Sweden)

Author keywords

Cardiovascular disease; Complications; Gender; Sex; Treatment; Type 2 diabetes

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ADIPONECTIN; ESTROGEN; GLUCOSE; GROWTH HORMONE; HYDROCORTISONE; INCRETIN; INSULIN; INSULIN GLARGINE; ISOPHANE INSULIN; LEPTIN; METFORMIN; SEX HORMONE; SEX HORMONE BINDING GLOBULIN; SOMATOMEDIN C; TESTOSTERONE;

BODY COMPOSITION; CARDIOVASCULAR RISK; DEPRESSION; DIABETIC RETINOPATHY; DISEASE COURSE; DRUG BLOOD LEVEL; DRUG SAFETY; DRUG TOLERABILITY; FOOT ULCER; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HIGH RISK PATIENT; HUMAN; KIDNEY DISEASE; LACTIC ACIDOSIS; LEG AMPUTATION; LIFESTYLE MODIFICATION; MALIGNANT NEOPLASTIC DISEASE; METABOLIC REGULATION; METABOLIC SYNDROME X; MORBIDITY; NEUROPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; ORAL GLUCOSE TOLERANCE TEST; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PRACTICE GUIDELINE; PREVALENCE; PROGNOSIS; QUALITY OF LIFE; REVIEW; SCREENING TEST; SEX DIFFERENCE; STOMACH PARESIS; SYSTEMATIC REVIEW; UNSPECIFIED SIDE EFFECT;

EID: 84907875980     PISSN: None     EISSN: 11787007     Source Type: Journal    
DOI: 10.2147/DMSO.S51301     Document Type: Review

References (171)

1. Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2(middle dot)7 million participants. Lancet. 2011;378(9785):31–40.
2. Agardh EE, Ahlbom A, Andersson T, et al. Work stress and low sense of coherence is associated with type 2 diabetes in middle-aged Swedish women. Diabetes Care. 2003;26(3):719–724.
3. Misra R, Lager J. Ethnic and gender differences in psychosocial factors, glycemic control, and quality of life among adult type 2 diabetic patients. J Diabetes Complications. 2009;23(1):54–64.
4. Shalev V, Chodick G, Heymann AD, Kokia E. Gender differences in healthcare utilization and medical indicators among patients with dia­betes. Public Health. 2005;119(1):45–49.
5. Tang YH, Pang SM, Chan MF, Yeung GS, Yeung VT. Health literacy, complication awareness, and diabetic control in patients with type 2 diabetes mellitus. J Adv Nurs. 2008;62(1):74–83.
6. Chiu CJ, Wray LA. Gender differences in functional limitations in adults living with type 2 diabetes: biobehavioral and psychosocial mediators. Ann Behav Med. 2011;41(1):71–82.
7. Nilsson PM, Theobald H, Journath G, Fritz T. Gender differences in risk factor control and treatment profile in diabetes: a study in 229 swedish primary health care centres. Scand J Prim Health Care. 2004;22(1): 27–31.
8. Wexler DJ, Grant RW, Meigs JB, Nathan DM, Cagliero E. Sex dispari­ties in treatment of cardiac risk factors in patients with type 2 diabetes. Diabetes Care. 2005;28(3):514–520.
9. Roche MM, Wang PP. Sex differences in all-cause and cardiovascular mortality, hospitalization for individuals with and without diabetes, and patients with diabetes diagnosed early and late. Diabetes Care. 2013;36(9):2582–2590.
10. Gregg EW, Gu Q, Cheng YJ, Narayan KM, Cowie CC. Mortality trends in men and women with diabetes, 1971 to 2000. Ann Intern Med. 2007;147(3):149–155.
11. Legato MJ, Gelzer A, Goland R, et al. Gender-specific care of the patient with diabetes: review and recommendations. Gend Med. 2006;3(2): 131–158.
12. Pilote L, Dasgupta K, Guru V, et al. A comprehensive view of sex-specific issues related to cardiovascular disease. CMAJ. 2007;176(6):S1–S44.
13. Pasquali R, Vicennati V, Gambineri A, Pagotto U. Sex-dependent role of glucocorticoids and androgens in the pathophysiology of human obesity. Int J Obes (Lond). 2008;32(12):1764–1779.
14. Mattsson C, Olsson T. Estrogens and glucocorticoid hormones in adipose tissue metabolism. Curr Med Chem. 2007;14(27):2918–2924.
15. Williams CM. Lipid metabolism in women. Proc Nutr Soc. 2004;63(1):153–160.
16. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their rela­tion to the metabolic syndrome. Endocr Rev. 2000;21(6):697–738.
17. Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism. 1991;40(12):1323–1326.
18. Regitz-Zagrosek V, Lehmkuhl E, Weickert MO. Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol. 2006;95(3):136–147.
19. Geer EB, Shen W. Gender differences in insulin resistance, body composition, and energy balance. Gend Med. 2009;6 Suppl 1:60–75.
20. Rebuffe-Scrive M, Bronnegard M, Nilsson A, Eldh J, Gustafsson JA, Bjorntorp P. Steroid hormone receptors in human adipose tissues. J Clin Endocrinol Metab. 1990;71(5):1215–1219.
21. Krotkiewski M, Bjorntorp P, Sjostrom L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983;72(3):1150–1162.
22. Regitz-Zagrosek V, Lehmkuhl E, Mahmoodzadeh S. Gender Aspects of the Role of the Metabolic Syndrome as a Risk Factor for Cardiovascular Disease. Gend Med. 2007;4(Suppl B):S162–S177.
23. Dallongeville J, Cottel D, Arveiler D, et al. The association of metabolic disorders with the metabolic syndrome is different in men and women. Ann Nutr Metab. 2004;48(1):43–50.
24. Szalat A, Raz I. Gender-specific care of diabetes mellitus: particular considerations in the management of diabetic women. Diabetes Obes Metab. 2008;10(12):1135–1156.
25. Hanefeld M, Koehler C, Fuecker K, et al. Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes study. Diabetes Care. 2003;26(3):868–874.
26. Goldstein BJ. Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol. 2002;90(5):3G–10G.
27. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–1053.
28. Gale EA, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44(1):3–15.
29. Sattar N. Gender aspects in type 2 diabetes mellitus and cardiometabolic risk. Best Pract Res Clin Endocrinol Metab. 2013;27(4):501–507.
30. Awa WL, Fach E, Krakow D, et al. Type 2 diabetes from pediatric to geriatric age: analysis of gender and obesity among 120,183 patients from the German/Austrian DPV database. Eur J Endocrinol. 2012;167(2):245–254.
31. Lewitt MS, Hilding A, Brismar K, Efendic S, Ostenson CG, Hall K. IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women. Eur J Endocrinol. 2010;163(2):233–242.
32. Lewitt MS, Hilding A, Ostenson CG, Efendic S, Brismar K, Hall K. Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men. Diabetologia. 2008;51(7):1135–1145.
33. Pomerleau J, McKeigue PM, Chaturvedi N. Relationships of fasting and postload glucose levels to sex and alcohol consumption. Are American Diabetes Association criteria biased against detection of diabetes in women? Diabetes Care. 1999;22(3):430–433.
34. Bjorntorp P. Visceral obesity: a “civilization syndrome”. Obes Res. 1993;1(3):206–222.
35. Arnetz L. The HPA Axis in Type 2 Diabetes – Some Aspects in Relation to Insulin Sensitivity, Beta-Cell Function and IGF-I/IGFBP-1 [doctoral thesis]. Stockholm: Department of Molecular Medicine and Surgery, Karolinska Institutet; 2014.
36. Federman DD. The biology of human sex differences. N Engl J Med. 2006;354(14):1507–1514.
37. Mayes JS, Watson GH. Direct effects of sex steroid hormones on adipose tissues and obesity. Obes Rev. 2004;5(4):197–216.
38. Meyer MR, Clegg DJ, Prossnitz ER, Barton M. Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors. Acta Physiol (Oxf). 2011;203(1):259–269.
39. Seidell JC, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt R. Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism. 1990;39(9):897–901.
40. Tibblin G, Adlerberth A, Lindstedt G, Bjorntorp P. The pituitary-gonadal axis and health in elderly men: a study of men born in 1913. Diabetes. 1996;45(11):1605–1609.
41. Marin P, Krotkiewski M, Bjorntorp P. Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues. Eur J Med. 1992;1(6):329–336.
42. Marin P, Holmang S, Gustafsson C, et al. Androgen treatment of abdominally obese men. Obes Res. 1993;1(4):245–251.
43. Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295(11):1288–1299.
44. Polderman KH, Gooren LJ, Asscheman H, Bakker A, Heine RJ. Induction of insulin resistance by androgens and estrogens. J Clin Endocrinol Metab. 1994;79(1):265–271.
45. Bjorntorp P. Neuroendocrine perturbations as a cause of insulin resistance. Diabetes Metab Res Rev. 1999;15(6):427–441.
46. Nandi A, Chen Z, Patel R, Poretsky L. Polycystic Ovary Syndrome. Endocrinol Metab Clin North Am. 2014;43(1):123–147.
47. Rincon J, Holmang A, Wahlstrom EO, et al. Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes. 1996;45(5):615–621.
48. Korhonen S, Hippelainen M, Vanhala M, Heinonen S, Niskanen L. The androgenic sex hormone profile is an essential feature of metabolic syndrome in premenopausal women: a controlled community-based study. Fertil Steril. 2003;79(6):1327–1334.
49. Barrett-Connor E, Holbrook TL. Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA. 1992;268(23):3333–3337.
50. Wake DJ, Strand M, Rask E, et al. Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity. Clin Endocrinol (Oxf). 2007;66(3):440–446.
51. Rajpathak SN, Gunter MJ, Wylie-Rosett J, et al. The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev. 2009;25(1):3–12.
52. Gatford KL, Egan AR, Clarke IJ, Owens PC. Sexual dimorphism of the somatotrophic axis. J Endocrinol. 1998;157(3):373–389.
53. Unden AL, Elofsson S, Knox S, Lewitt MS, Brismar K. IGF-I in a normal population: Relation to psychosocial factors. Clin Endocrinol (Oxf). 2002;57(6):793–803.
54. Hilding A, Brismar K, Degerblad M, Thoren M, Hall K. Altered rela­tion between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects. J Clin Endocrinol Metab. 1995;80(9):2646–2652.
55. Baxter RC. Insulin-like growth factor (IGF)-binding proteins: interac­tions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab. 2000;278(6):E967–E976.
56. Unden AL, Elofsson S, Brismar K. Gender differences in the relation of insulin-like growth factor binding protein-1 to cardiovascular risk factors: A population-based study. Clin Endocrinol (Oxf). 2005;63(1):94–102.
57. Cardim HJ, Lopes CM, Giannella-Neto D, da Fonseca AM, Pinotti JA. The insulin-like growth factor-I system and hormone replacement therapy. Fertil Steril. 2001;75(2):282–287.
58. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996;271(18):10697–10703.
59. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resis­tance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116(7):1784–1792.
60. Halleux CM, Takahashi M, Delporte ML, et al. Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun. 2001;288(5):1102–1107.
61. Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 2001;50(9):2094–2099.
62. Nishizawa H, Shimomura I, Kishida K, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002;51(9):2734–2741.
63. Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: Close association with insulin resis­tance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5): 1930–1935.
64. Cnop M, Havel PJ, Utzschneider KM, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia. 2003;46(4):459–469.
65. Spranger J, Kroke A, Mohlig M, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003;361(9353):226–228.
66. Dekker JM, Funahashi T, Nijpels G, et al. Prognostic value of adiponectin for cardiovascular disease and mortality. J Clin Endocrinol Metab. 2008;93(4):1489–1496.
67. Unger RH. The physiology of cellular liporegulation. Annu Rev Physiol. 2003;65:333–347.
68. Barrett-Connor E. Sex differences in coronary heart disease: Why are women so superior? The 1995 Ancel Keys Lecture. Circulation. 1997;95(1):252–264.
69. Thomas T, Burguera B, Melton LJ III, et al. Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women. Metabolism. 2000;49(10):1278–1284.
70. Soderberg S, Stegmayr B, Stenlund H, et al. Leptin, but not adiponectin, predicts stroke in males. J Intern Med. 2004;256(2):128–136.
71. Wallace AM, McMahon AD, Packard CJ, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001;104(25):3052–3056.
72. Piemonti L, Calori G, Mercalli A, et al. Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality. Diabetes Care. 2003;26(10):2883–2889.
73. Washington EL, Shen JJ. Gender discrepancies in the level of dis­ease progression in hospitalized patients with diabetes. Manag Care Interface. 2006;19(10):21–25.
74. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med. 2008;358(24):2545–2559.
75. ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–2572.
76. No authors listed. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854–865.
77. Viberti G, Kahn SE, Greene DA, et al. A diabetes outcome pro­gression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Diabetes Care. 2002;25(10):1737–1743.
78. McGill JB, Vlajnic A, Knutsen PG, Recklein C, Rimler M, Fisher SJ. Effect of gender on treatment outcomes in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2013;102(3):167–174.
79. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.
80. Perreault L, Ma Y, Dagogo-Jack S, et al. Sex differences in diabetes risk and the effect of intensive lifestyle modification in the Diabetes Prevention Program. Diabetes Care. 2008;31(7):1416–1421.
81. Tuthill A, McKenna MJ, O’Shea D, McKenna TJ. Weight changes in type 2 diabetes and the impact of gender. Diabetes Obes Metab. 2008;10(9):726–732.
82. Hu FB, Stampfer MJ, Solomon C, et al. Physical activity and risk for cardiovascular events in diabetic women. Ann Intern Med. 2001;134(2):96–105.
83. Loprinzi PD, Pariser G. Physical activity intensity and biological markers among adults with diabetes: considerations by age and gender. J Diabetes Complications. 2013;27(2):134–140.
84. Penno G, Solini A, Bonora E, et al. Gender differences in cardiovascular disease risk factors, treatments and complications in patients with type 2 diabetes: the RIACE Italian multicentre study. J Intern Med. 2013;274(2):176–191.
85. Kramer HU, Ruter G, Schottker B, et al. Gender differences in healthcare utilization of patients with diabetes. Am J Manag Care. 2012;18(7):362–369.
86. Kramer HU, Raum E, Ruter G, et al. Gender disparities in diabetes and coronary heart disease medication among patients with type 2 diabetes: results from the DIANA study. Cardiovasc Diabetol. 2012;11:88.
87. Kautzky-Willer A, Kamyar MR, Gerhat D, et al. Sex-specific differences in metabolic control, cardiovascular risk, and interventions in patients with type 2 diabetes mellitus. Gend Med. 2010;7(6):571–583.
88. Karim A, Slater M, Bradford D, et al. Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and met­formin. Effect of body weight, gender, and race on systemic exposures of each drug. J Clin Pharmacol. 2007;47(1):37–47.
89. Lyons MR, Peterson LR, McGill JB, et al. Impact of sex on the heart’s metabolic and functional responses to diabetic therapies. Am J Physiol Heart Circ Physiol. 2013;305(11):H1584–H1591.
90. Walker EA, Molitch M, Kramer MK, et al. Adherence to preventive medications: predictors and outcomes in the Diabetes Prevention Program. Diabetes Care. 2006;29(9):1997–2002.
91. Biradar V, Moran JL, Peake SL, Peter JV. Metformin-associated lactic acidosis (MALA): clinical profile and outcomes in patients admitted to the intensive care unit. Crit Care Resusc. 2010;12(3):191–195.
92. Pongwecharak J, Tengmeesri N, Malanusorn N, Panthong M, Pawangkapin N. Prescribing metformin in type 2 diabetes with a contraindication: prevalence and outcome. Pharm World Sci. 2009;31(4):481–486.
93. Benz V, Kintscher U, Foryst-Ludwig A. Sex-specific differences in Type 2 Diabetes Mellitus and dyslipidemia therapy: PPAR agonists. Handb Exp Pharmacol. 2012;(214):387–410.
94. Dorkhan M, Magnusson M, Frid A, Grubb A, Groop L, Jovinge S. Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of patients with type 2 diabetes. J Intern Med. 2006;260(2): 125–133.
95. Akazawa S, Sun F, Ito M, Kawasaki E, Eguchi K. Efficacy of troglitazone on body fat distribution in type 2 diabetes. Diabetes Care. 2000;23(8):1067–1071.
96. Flory JH, Small DS, Cassano PA, Brillon DJ, Mushlin AI, Hennessy S. Comparative effectiveness of oral diabetes drug combinations in reducing glycosylated hemoglobin. J Comp Eff Res. 2014;3(1): 29–39.
97. Esteghamati A, Noshad S, Rabizadeh S, Ghavami M, Zandieh A, Nakhjavani M. Comparative effects of metformin and pioglitazone on omentin and leptin concentrations in patients with newly diagnosed diabetes: a randomized clinical trial. Regul Pept. 2013;182:1–6.
98. Vlckova V, Cornelius V, Kasliwal R, Wilton L, Shakir S. Hypoglycaemia with pioglitazone: analysis of data from the Prescription-Event Monitoring study. J Eval Clin Pract. 2010;16(6):1124–1128.
99. Arnetz L, Dorkhan M, Alvarsson M, Brismar K, Ekberg NR. Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes. Acta Diabetologica. 2014;51(2):185–192.
100. Wheeler S, Moore K, Forsberg CW, et al. Mortality among veterans with type 2 diabetes initiating metformin, sulfonylurea or rosiglitazone monotherapy. Diabetologia. Epub June 25, 2013.
101. Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012;124(4):21–32.
102. Buysschaert M, Preumont V, Oriot PR, et al. One-year metabolic outcomes in patients with type 2 diabetes treated with exenatide in routine practice. Diabetes Metab. 2010;36(5):381–388.
103. Damholt B, Golor G, Wierich W, Pedersen P, Ekblom M, Zdravkovic M. An open-label, parallel group study investigating the effects of age and gender on the pharmacokinetics of the once-daily glucagon-like peptide-1 analogue liraglutide. J Clin Pharmacol. 2006;46(6):635–641.
104. Anichini R, Cosimi S, Di Carlo A, et al. Gender difference in response predictors after 1-year exenatide therapy twice daily in type 2 diabetic patients: a real world experience. Diabetes Metab Syndr Obes. 2013;6:123–129.
105. He YL. Clinical pharmacokinetics and pharmacodynamics of vildagliptin. Clin Pharmacokinet. 2012;51(3):147–162.
106. Deacon CF, Holst JJ. Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther. 2009;26(5):488–499.
107. Kajiwara A, Saruwatari J, Sakata M, et al. Risk factors for adverse symptoms during dipeptidyl peptidase-IV inhibitor therapy: a questionnaire-based study carried out by the Japan Pharmaceutical Association Drug Event Monitoring project in Kumamoto Prefecture. Drug Saf. 2013;36(10):981–987.
108. Krepinsky J, Ingram AJ, Clase CM. Prolonged sulfonylurea-induced hypoglycemia in diabetic patients with end-stage renal disease. Am J Kidney Dis. 2000;35(3):500–505.
109. Marbury T, Huang WC, Strange P, Lebovitz H. Repaglinide versus glyburide: a one-year comparison trial. Diabetes Res Clin Pract. 1999;43(3):155–166.
110. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014;53(1):17–27.
111. Amiel SA, Maran A, Powrie JK, Umpleby AM, Macdonald IA. Gender differences in counterregulation to hypoglycaemia. Diabetologia. 1993;36(5):460–464.
112. Diamond MP, Jones T, Caprio S, et al. Gender influences counterregulatory hormone responses to hypoglycemia. Metabolism. 1993;42(12):1568–1572.
113. Korner A, Wabitsch M, Seidel B, et al. Adiponectin expression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components of high molecular weight. Biochem Biophys Res Commun. 2005;337(2):540–550.
114. Wandell PE, Gafvels C. Patients with type 2 diabetes aged 35–64 years at four primary health care centres in Stockholm County, Sweden. Prevalence and complications in relation to gender and socio-economic status. Diabetes Res Clin Pract. 2004;63(3):195–203.
115. Kajiwara A, Miyagawa H, Saruwatari J, et al. Gender differences in the incidence and progression of diabetic retinopathy among Japanese patients with type 2 diabetes mellitus: A clinic-based retrospective longitudinal study. Diabetes Res Clin Pract. 2014;103(3):e7–e10.
116. Afzal N, Zaman S, Asghar A, et al. Negative Association of Serum IL-6 and IL-17 with Type-II Diabetes Retinopathy. Iran J Immunol. 2014;11(1):40–48.
117. Kostev K, Rathmann W. Diabetic retinopathy at diagnosis of type 2 diabetes in the UK: a database analysis. Diabetologia. 2013;56(1): 109–111.
118. Liu JH, Tung TH, Tsai ST, et al. A community-based epidemiologic study of gender differences in the relationship between insulin resistance/beta-cell dysfunction and diabetic retinopathy among type 2 diabetic patients in Kinmen, Taiwan. Ophthalmologica. 2006;220(4):252–258.
119. Aaberg ML, Burch DM, Hud ZR, Zacharias MP. Gender differences in the onset of diabetic neuropathy. J Diabetes Complications. 2008;22(2):83–87.
120. Nakhjavani M, Morteza A, Jenab Y, et al. Gender difference in albuminuria and ischemic heart disease in type 2 diabetes. Clin Med Res. 2012;10(2):51–56.
121. Dickman R, Wainstein J, Glezerman M, Niv Y, Boaz M. Gender aspects suggestive of gastroparesis in patients with diabetes mellitus: a cross-sectional survey. BMC Gastroenterol. 2014;14(1):34.
122. Peek ME. Gender differences in diabetes-related lower extremity amputations. Clin Orthop Relat Res. 2011;469(7):1951–1955.
123. Bruun C, Siersma V, Guassora AD, Holstein P, de Fine Olivarius N. Amputations and foot ulcers in patients newly diagnosed with type 2 diabetes mellitus and observed for 19 years. The role of age, gender and co-morbidity. Diabet Med. 2013;30(8):964–972.
124. Janghorbani M, Hedley AJ, Jones RB, Zhianpour M, Gilmour WH. Gender differential in all-cause and cardiovascular disease mortality. Int J Epidemiol. 1993;22(6):1056–1063.
125. Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab. 2003;88(6):2404–2411.
126. Welty FK. Women and cardiovascular risk. American J Cardiol. 2001;88(7b):48J–52J.
127. Kalyani RR, Lazo M, Ouyang P, et al. Gender Differences in Diabetes and Risk of Incident Coronary Artery Disease in Healthy Young and Middle-Aged Adults. Diabetes Care. 2014;37(3):830–838.
128. Lundberg V, Stegmayr B, Asplund K, Eliasson M, Huhtasaari F. Dia­betes as a risk factor for myocardial infarction: population and gender perspectives. J Intern Med. 1997;241(6):485–492.
129. Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med. 1991;151(6):1141–1147.
130. Wu YT, Chien CL, Wang SY, Yang WS, Wu YW. Gender differences in myocardial perfusion defect in asymptomatic postmenopausal women and men with and without diabetes mellitus. J Womens Health (Larchmt). 2013;22(5):439–444.
131. Hung MJ, Hsu KH, Hu WS, Chang NC, Hung MY. C-reactive protein for predicting prognosis and its gender-specific associations with diabetes mellitus and hypertension in the development of coronary artery spasm. PloS One. 2013;8(10):77655.
132. Martinez-Selles M, Doughty RN, Poppe K, et al. Gender and survival in patients with heart failure: interactions with diabetes and aetiology. Results from the MAGGIC individual patient meta-analysis. Eur J Heart Fail. 2012;14(5):473–479.
133. Legato MJ, editors. Gender and its Impact of Risk Factors for Cardiovascular Disease. In: Principles of Gender-Specific Medicine. San Diego, CA: Elsevier Academic Press; 2004; No 1.
134. Hypertension in Diabetes Study (HDS): I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications. J Hypertens. 1993;11(3):309–317.
135. Elveback LR, Connolly DC, Melton LJ III. Coronary heart disease in residents of Rochester, Minnesota. VII. Incidence, 1950 through 1982. Mayo Clin Proc. 1986;61(11):896–900.
136. Walden CE, Knopp RH, Wahl PW, Beach KW, Strandness E Jr. Sex differences in the effect of diabetes mellitus on lipoprotein triglyceride and cholesterol concentrations. N Engl J Med. 1984;311(15):953–959.
137. Mosca L, Manson JE, Sutherland SE, Langer RD, Manolio T, Barrett-Connor E. Cardiovascular disease in women: a statement for healthcare professionals from the American Heart Association. Writing Group. Circulation. 1997;96(7):2468–2482.
138. Schroeder EB, Bayliss EA, Daugherty SL, Steiner JF. Gender differences in cardiovascular risk factors in incident diabetes. Women’s Health Issues. 2014;24(1):e61–e68.
139. Hu G, Jousilahti P, Qiao Q, Katoh S, Tuomilehto J. Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction. Diabetologia. 2005;48(5):856–861.
140. Hu G, DECODE Study Group. Gender difference in all-cause and cardiovascular mortality related to hyperglycaemia and newly-diagnosed diabetes. Diabetologia. 2003;46(5):608–617.
141. Kanaya AM, Grady D, Barrett-Connor E. Explaining the sex differ­ence in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med. 2002;162(15): 1737–1745.
142. Goldschmid MG, Barrett-Connor E, Edelstein SL, Wingard DL, Cohn BA, Herman WH. Dyslipidemia and ischemic heart disease mortality among men and women with diabetes. Circulation. 1994;89(3):991–997.
143. Lee C, Joseph L, Colosimo A, Dasgupta K. Mortality in diabetes compared with previous cardiovascular disease: a gender-specific meta-analysis. Diabetes Metab. 2012;38(5):420–427.
144. Shekelle PG, Rich MW, Morton SC, et al. Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. J Am Coll Cardiol. 2003;41(9):1529–1538.
145. Walsh JM, Pignone M. Drug treatment of hyperlipidemia in women. JAMA. 2004;291(18):2243–2252.
146. Shigematsu E, Yamakawa T, Taguri M, et al. Efficacy of ezetimibe is associated with gender and baseline lipid levels in patients with type 2 diabetes. J Atheroscler Thromb. 2012;19(9):846–853.
147. Howard BV, Cowan LD, Go O, Welty TK, Robbins DC, Lee ET. Adverse effects of diabetes on multiple cardiovascular disease risk factors in women. The Strong Heart Study. Diabetes Care. 1998;21(8):1258–1265.
148. Franconi F, Campesi I, Occhioni S, Tonolo G. Sex-gender differences in diabetes vascular complications and treatment. Endocr Metab Immune Disord Drug Targets. 2012;12(2):179–196.
149. Gilbert J, Raboud J, Zinman B. Meta-analysis of the effect of diabetes on restenosis rates among patients receiving coronary angioplasty stenting. Diabetes Care. 2004;27(4):990–994.
150. Jacobs AK, Johnston JM, Haviland A, et al. Improved outcomes for women undergoing contemporary percutaneous coronary intervention: a report from the National Heart, Lung, and Blood Institute Dynamic registry. J Am Coll Cardiol. 2002;39(10):1608–1614.
151. Mehilli J, Kastrati A, Bollwein H, et al. Gender and restenosis after coronary artery stenting. Eur Heart J. 2003;24(16):1523–1530.
152. Legato MJ. Dyslipidemia, gender, and the role of high-density lipoprotein cholesterol: implications for therapy. Am J Cardiol. 2000;86(12A):15L–18L.
153. Orchard TJ. The impact of gender and general risk factors on the occurrence of atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus. Ann Med. 1996;28(4):323–333.
154. Steinberg HO, Paradisi G, Cronin J, et al. Type II diabetes abrogates sex differences in endothelial function in premenopausal women. Circulation. 2000;101(17):2040–2046.
155. Chan P, Pan WH. Coagulation activation in type 2 diabetes mellitus: the higher coronary risk of female diabetic patients. Diabet Med. 1995;12(6):504–507.
156. Mascarenhas-Melo F, Marado D, Palavra F, et al. Diabetes abrogates sex differences and aggravates cardiometabolic risk in postmenopausal women. Cardiovasc Diabetol. 2013;12:61.
157. Nakhjavani M, Morteza A, Meysamie A, et al. Serum heat shock protein 70 and oxidized LDL in patients with type 2 diabetes: does sex matter? Cell Stress Chaperones. 2011;16(2):195–201.
158. Schenck-Gustafsson K. Diagnosis of cardiovascular disease in women. Menopause Int. 2007;13(1):19–22.
159. Zelenko Z, Gallagher EJ. Diabetes and Cancer. Endocrinol Metab Clin North Am. 2014;43(1):167–185.
160. Vestergaard P, Starup-Linde J. Diabetes, cancer and treatment – a mini-review. Curr Drug Saf. 2013;8(5):292–295.
161. Kramer HU, Muller H, Stegmaier C, Rothenbacher D, Raum E, Brenner H. Type 2 diabetes mellitus and gender-specific risk for colorectal neoplasia. Eur J Epidemiol. 2012;27(5):341–347.
162. Tseng CH. Diabetes and risk of bladder cancer: a study using the National Health Insurance database in Taiwan. Diabetologia. 2011;54(8):2009–2015.
163. Chiou WK, Hwang JS, Hsu KH, Lin JD. Diabetes mellitus increased mortality rates more in gender-specific than in nongender-specific cancer patients: a retrospective study of 149,491 patients. Exp Diabetes Res. 2012;2012:701643.
164. Sun GE, Wells BJ, Yip K, et al. Gender-specific effects of oral hypoglycaemic agents on cancer risk in type 2 diabetes mellitus. Diabetes Obes Metab. 2014;16(3):276–283.
165. Siddiqui MA, Khan MF, Carline TE. Gender differences in living with diabetes mellitus. Materia Sociomed. 2013;25(2):140–142.
166. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001;24(6):1069–1078.
167. Muller G, Hartwig S, Greiser KH, et al. Gender differences in the association of individual social class and neighbourhood unem­ployment rate with prevalent type 2 diabetes mellitus: a cross-sectional study from the DIAB-CORE consortium. BMJ Open. 2013;3(6):1–11.
168. Eriksson AK, Ekbom A, Granath F, Hilding A, Efendic S, Ostenson CG. Psychological distress and risk of pre-diabetes and Type 2 diabetes in a prospective study of Swedish middle-aged men and women. Diabetic Med. 2008;25(7):834–842.
169. Eriksson AK, van den Donk M, Hilding A, Ostenson CG. Work stress, sense of coherence, and risk of type 2 diabetes in a prospective study of middle-aged Swedish men and women. Diabetes Care. 2013;36(9):2683–2689.
170. Svenningsson I, Bjorkelund C, Marklund B, Gedda B. Anxiety and depression in obese and normal-weight individuals with diabetes type 2: a gender perspective. Scand J Caring Sci. 2012;26(2): 349–354.
171. Nau DP, Aikens JE, Pacholski AM. Effects of gender and depression on oral medication adherence in persons with type 2 diabetes mellitus. Gend Med. 2007;4(3):205–213.