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Diabetologia

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01-08-2011 | Article

Sex-related differences in the long-term risk of microvascular complications by age at onset of type 1 diabetes

Authors: V. Harjutsalo, C. Maric, C. Forsblom, L. Thorn, J. Wadén, P. H. Groop, on behalf of the FinnDiane Study Group

Published in: Diabetologia | Issue 8/2011

Abstract

Aims/hypothesis

This study examined sex-related differences in the cumulative risk of proliferative retinopathy (PR) and end-stage renal disease (ESRD) over 40 years of duration of type 1 diabetes according to age at diabetes onset.

Methods

We assessed 4,416 patients from the Finnish Diabetic Nephropathy Study population. Kaplan–Meier analysis was used to provide cumulative incidence rates and Cox regression analyses for HRs.

Results

There were no sex-related differences in the cumulative incidence of ESRD in patients diagnosed with type 1 diabetes between 0 to 4 and 5 to 9 years. Thereafter the risk started to diverge. The cumulative incidence of ESRD in patients diagnosed between 10 to 14 and ≥15 years was 17.4% (95% CI 13.4–21.2) and 13.0% (9.6–16.2) respectively in women, while in men it was 32.2% (28.0–36.1) and 24.6% (20.8–28.1) respectively. The respective HRs were (onset at 10 to 14 years) 1.9 (p < 0.0001) and (onset at ≥15 years) 1.8 (p < 0.001), respectively. There was no difference in the risk of PR between men and women diagnosed between 0 and 4 years of age, but progressive sex-related differences in the cumulative incidence of PR were observed with increasing age at onset. The HRs for men in the age-at-onset groups 5 to 9, 10 to 14 and ≥15 years of age were 1.3 (95% CI 1.0–1.6), 1.3 (1.1–1.6) and 2.1 (1.6–2.6) compared with women in these groups, respectively.

Conclusions/interpretation

The difference between the sexes with regard to risk of diabetic microvascular complications is highly dependent on the age at onset of diabetes. The risk of ESRD and PR risk doubled in men compared with women when age at onset was ≥15 years.

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Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T (1983) Diabetic nephropathy in type 1 (insulin-dependent) diabetes: an epidemiological study. Diabetologia 25:496–501PubMedCrossRef

Jacobsen P, Rossing K, Tarnow L et al (1999) Progression of diabetic nephropathy in normotensive type 1 diabetic patients. Kidney Int (Suppl) 71:S101–S105CrossRef

Schultz CJ, Konopelska-Bahu T, Dalton RN et al (1999) Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group. Diabetes Care 22:495–502PubMedCrossRef

Svensson M, Nyström L, Schon S, Dahlquist G (2006) Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study. Diabetes Care 29:538–542PubMedCrossRef

Raile K, Galler A, Hofer S et al (2007) Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care 30:2523–2528PubMedCrossRef

Harjutsalo V, Katoh S, Sarti C, Tajima N, Tuomilehto J (2004) Population-based assessment of familial clustering of diabetic nephropathy in type 1 diabetes. Diabetes 53:2449–2454PubMedCrossRef

Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE (2008) The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII. The twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 115:1859–1868PubMedCrossRef

Donaghue KC, Fairchild JM, Craig ME et al (2003) Do all prepubertal years of diabetes duration contribute equally to diabetes complications? Diabetes Care 26:1224–1229PubMedCrossRef

Hietala K, Harjutsalo V, Forsblom C, Summanen P, Groop PH (2010) Age at onset and the risk of proliferative retinopathy in type 1 diabetes. Diabetes Care 33:1315–1319PubMedCrossRef

10.

Rudberg S, Ullman E, Dahlquist G (1993) Relationship between early metabolic control and the development of microalbuminuria—a longitudinal study in children with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 36:1309–1314PubMedCrossRef

11.

Mauer M, Drummond K (2002) The early natural history of nephropathy in type 1 diabetes: I. Study design and baseline characteristics of the study participants. Diabetes 51:1572–1579PubMedCrossRef

12.

Drummond KN, Kramer MS, Suissa S et al (2003) Effects of duration and age at onset of type 1 diabetes on preclinical manifestations of nephropathy. Diabetes 52:1818–1824PubMedCrossRef

13.

Janner M, Knill SE, Diem P, Zuppinger KA, Mullis PE (1994) Persistent microalbuminuria in adolescents with type I (insulin-dependent) diabetes mellitus is associated to early rather than late puberty. Results of a prospective longitudinal study. Eur J Pediatr 153:403–408PubMedCrossRef

14.

Klein R, Klein BE, Moss SE, Cruickshanks KJ (1998) The Wisconsin epidemiologic study of diabetic retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 105:1801–1815PubMedCrossRef

15.

Kostraba JN, Dorman JS, Orchard TJ et al (1989) Contribution of diabetes duration before puberty to development of microvascular complications in IDDM subjects. Diabetes Care 12:686–693PubMedCrossRef

16.

Lawson ML, Sochett EB, Chait PG, Balfe JW, Daneman D (1996) Effect of puberty on markers of glomerular hypertrophy and hypertension in IDDM. Diabetes 45:51–55PubMedCrossRef

17.

The Epidemiology of Diabetes Intervention and Complications (EDIC) Study (2003) Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. JAMA 290:2159–2167CrossRef

18.

Kauffman AS (2010) Coming of age in the kisspeptin era: sex differences, development, and puberty. Mol Cell Endocrinol 324:51–63PubMedCrossRef

19.

Harjutsalo V, Sjoberg L, Tuomilehto J (2008) Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 371:1777–1782PubMedCrossRef

20.

Soltesz G, Patterson CC, Dahlquist G (2007) Worldwide childhood type 1 diabetes incidence—what can we learn from epidemiology? Pediatr Diabetes 8(Suppl 6):6–14PubMedCrossRef

21.

Zhang H, Xia W, Yu Q et al (2008) Increasing incidence of type 1 diabetes in children aged 0–14 years in Harbin, China (1990–2000). Prim Care Diabetes 2:121–126PubMedCrossRef

22.

Lammi N, Taskinen O, Moltchanova E et al (2007) A high incidence of type 1 diabetes and an alarming increase in the incidence of type 2 diabetes among young adults in Finland between 1992 and 1996. Diabetologia 50:1393–1400PubMedCrossRef

23.

Ostman J, Lonnberg G, Arnqvist HJ et al (2008) Gender differences and temporal variation in the incidence of type 1 diabetes: results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983–2002. J Intern Med 263:386–394PubMedCrossRef

24.

Thorn LM, Forsblom C, Fagerudd J et al (2005) Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane Study). Diabetes Care 28:2019–2024PubMedCrossRef

25.

Monti MC, Lonsdale JT, Montomoli C, Montross R, Schlag E, Greenberg DA (2007) Familial risk factors for microvascular complications and differential male–female risk in a large cohort of American families with type 1 diabetes. J Clin Endocrinol Metab 92:4650–4655PubMedCrossRef

26.

Harvey JN, Allagoa B (2004) The long-term renal and retinal outcome of childhood-onset type 1 diabetes. Diabet Med 21:26–31PubMedCrossRef

27.

Mollsten A, Svensson M, Waernbaum I et al (2010) Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. Diabetes 59:1803–1808PubMedCrossRef

28.

El-Osta A, Brasacchio D, Yao D et al (2008) Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 205:2409–2417PubMedCrossRef

29.

Kaminsky Z, Wang SC, Petronis A (2006) Complex disease, gender and epigenetics. Ann Med 38:530–544PubMedCrossRef

30.

Cummings EA, Sochett EB, Dekker MG, Lawson ML, Daneman D (1998) Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes. Diabetes 47:1341–1346PubMedCrossRef

31.

Amin R, Schultz C, Ong K et al (2003) Low IGF-I and elevated testosterone during puberty in subjects with type 1 diabetes developing microalbuminuria in comparison to normoalbuminuric control subjects: the Oxford Regional Prospective Study. Diabetes Care 26:1456–1461PubMedCrossRef

32.

Maric C, Forsblom C, Thorn L, Waden J, Groop PH (2010) Association between testosterone, estradiol and sex hormone binding globulin levels in men with type 1 diabetes with nephropathy. Steroids 75:772–778PubMedCrossRef

33.

Haffner SM, Klein R, Moss SE, Klein BE (1993) Sex hormones and the incidence of severe retinopathy in male subjects with type I diabetes. Ophthalmology 100:1782–1786PubMed

34.

Haffner SM, Klein R, Dunn JF, Moss SE, Klein BE (1990) Increased testosterone in type I diabetic subjects with severe retinopathy. Ophthalmology 97:1270–1274PubMed

35.

Chaurasia RK, Singh R, Agrawal JK, Maurya OP (1993) Sex hormones and diabetic retinopathy. Ann Ophthalmol 25:227–230PubMed

36.

Mankhey RW, Bhatti F, Maric C (2005) 17beta-Estradiol replacement improves renal function and pathology associated with diabetic nephropathy. Am J Physiol Renal Physiol 288:F399–F405PubMedCrossRef

37.

Keck M, Romero-Aleshire MJ, Cai Q, Hoyer PB, Brooks HL (2007) Hormonal status affects the progression of STZ-induced diabetes and diabetic renal damage in the VCD mouse model of menopause. Am J Physiol Renal Physiol 293:F193–F199PubMedCrossRef

38.

Kaja S, Yang SH, Wei J et al (2003) Estrogen protects the inner retina from apoptosis and ischemia-induced loss of Vesl-1L/Homer 1c immunoreactive synaptic connections. Invest Ophthalmol Vis Sci 44:3155–3162PubMedCrossRef

39.

Maric C, Sullivan S (2008) Estrogens and the diabetic kidney. Gend Med 5(Suppl A):S103–S113PubMedCrossRef

40.

Xu Q, Wells CC, Garman JH, Asico L, Escano CS, Maric C (2008) Imbalance in sex hormone levels exacerbates diabetic renal disease. Hypertension 51:1218–1224PubMedCrossRef

Title: Sex-related differences in the long-term risk of microvascular complications by age at onset of type 1 diabetes
Authors: V. Harjutsalo
C. Maric
C. Forsblom
L. Thorn
J. Wadén
P. H. Groop
on behalf of the FinnDiane Study Group
Publication date: 01-08-2011
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 8/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2144-2

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