Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study

Rianneke de Ritter; Simone J S Sep; Carla J H van der Kallen; Marleen M J van Greevenbroek; Marit de Jong; Rimke C Vos; Michiel L Bots; Jos P H Reulen; Alfons J H M Houben; Carroll A B Webers; Tos T J M Berendschot; Pieter C Dagnelie; Simone J P M Eussen; Miranda T Schram; Annemarie Koster; Sanne A E Peters; Coen D A Stehouwer

doi:10.1186/s12933-021-01290-x

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study

Rianneke de Ritter^*, Simone J S Sep, Carla J H van der Kallen, Marleen M J van Greevenbroek, Marit de Jong, Rimke C Vos, Michiel L Bots, Jos P H Reulen, Alfons J H M Houben, Carroll A B Webers, Tos T J M Berendschot, Pieter C Dagnelie, Simone J P M Eussen, Miranda T Schram, Annemarie Koster, Sanne A E Peters, Coen D A Stehouwer

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures.

METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.

RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.

CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

Original language	English
Article number	102
Number of pages	15
Journal	Cardiovascular Diabetology
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12933-021-01290-x
Publication status	Published - 7 May 2021

Keywords

DETERMINANTS
DIET
Epidemiology
INDIVIDUALS
MELLITUS
Microvascular complications
NEPHROPATHY
Nephropathy
Neuropathy
PERIPHERAL NEUROPATHY
PREVALENCE
RETINOPATHY
RISK-FACTORS
Retinopathy
Sex
Sex difference
Type 2 diabetes
WOMEN
Women

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de Ritter, R., Sep, S. J. S., van der Kallen, C. J. H., van Greevenbroek, M. M. J., de Jong, M., Vos, R. C., Bots, M. L., Reulen, J. P. H., Houben, A. J. H. M., Webers, C. A. B., Berendschot, T. T. J. M., Dagnelie, P. C., Eussen, S. J. P. M., Schram, M. T., Koster, A., Peters, S. A. E., & Stehouwer, C. D. A. (2021). Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study. Cardiovascular Diabetology, 20(1), Article 102. https://doi.org/10.1186/s12933-021-01290-x

@article{5f13af5ea2e547058a955d3a3ff7ae8c,

title = "Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study",

abstract = "BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures.METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.",

keywords = "DETERMINANTS, DIET, Epidemiology, INDIVIDUALS, MELLITUS, Microvascular complications, NEPHROPATHY, Nephropathy, Neuropathy, PERIPHERAL NEUROPATHY, PREVALENCE, RETINOPATHY, RISK-FACTORS, Retinopathy, Sex, Sex difference, Type 2 diabetes, WOMEN, Women",

author = "{de Ritter}, Rianneke and Sep, {Simone J S} and {van der Kallen}, {Carla J H} and {van Greevenbroek}, {Marleen M J} and {de Jong}, Marit and Vos, {Rimke C} and Bots, {Michiel L} and Reulen, {Jos P H} and Houben, {Alfons J H M} and Webers, {Carroll A B} and Berendschot, {Tos T J M} and Dagnelie, {Pieter C} and Eussen, {Simone J P M} and Schram, {Miranda T} and Annemarie Koster and Peters, {Sanne A E} and Stehouwer, {Coen D A}",

note = "Funding Information: This study was supported by ZonMw (Project No. 849200001), the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs (Grant 31O.041), Stichting De Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), CARIM, School for Cardiovascular Diseases (Maastricht, the Netherlands), School CAPHRI, Care and Public Health Research Institute (Maastricht, the Netherlands), NUTRIM, School of Nutrition and Translational Research in Metabolism (Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), Health Foundation Limburg (Maastricht, the Netherlands) and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands) and Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = may,

day = "7",

doi = "10.1186/s12933-021-01290-x",

language = "English",

volume = "20",

journal = "Cardiovascular Diabetology",

issn = "1475-2840",

publisher = "BioMed Central Ltd",

number = "1",

}

de Ritter, R , Sep, SJS , van der Kallen, CJH , van Greevenbroek, MMJ, de Jong, M, Vos, RC, Bots, ML, Reulen, JPH, Houben, AJHM , Webers, CAB , Berendschot, TTJM , Dagnelie, PC , Eussen, SJPM , Schram, MT , Koster, A, Peters, SAE & Stehouwer, CDA 2021, 'Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study', Cardiovascular Diabetology, vol. 20, no. 1, 102. https://doi.org/10.1186/s12933-021-01290-x

TY - JOUR

T1 - Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function

T2 - The Maastricht Study

AU - de Ritter, Rianneke

AU - Sep, Simone J S

AU - van der Kallen, Carla J H

AU - van Greevenbroek, Marleen M J

AU - de Jong, Marit

AU - Vos, Rimke C

AU - Bots, Michiel L

AU - Reulen, Jos P H

AU - Houben, Alfons J H M

AU - Webers, Carroll A B

AU - Berendschot, Tos T J M

AU - Dagnelie, Pieter C

AU - Eussen, Simone J P M

AU - Schram, Miranda T

AU - Koster, Annemarie

AU - Peters, Sanne A E

AU - Stehouwer, Coen D A

N1 - Funding Information: This study was supported by ZonMw (Project No. 849200001), the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs (Grant 31O.041), Stichting De Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), CARIM, School for Cardiovascular Diseases (Maastricht, the Netherlands), School CAPHRI, Care and Public Health Research Institute (Maastricht, the Netherlands), NUTRIM, School of Nutrition and Translational Research in Metabolism (Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), Health Foundation Limburg (Maastricht, the Netherlands) and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands) and Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands). Publisher Copyright: © 2021, The Author(s).

PY - 2021/5/7

Y1 - 2021/5/7

N2 - BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures.METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

AB - BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures.METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

KW - DETERMINANTS

KW - DIET

KW - Epidemiology

KW - INDIVIDUALS

KW - MELLITUS

KW - Microvascular complications

KW - NEPHROPATHY

KW - Nephropathy

KW - Neuropathy

KW - PERIPHERAL NEUROPATHY

KW - PREVALENCE

KW - RETINOPATHY

KW - RISK-FACTORS

KW - Retinopathy

KW - Sex

KW - Sex difference

KW - Type 2 diabetes

KW - WOMEN

KW - Women

U2 - 10.1186/s12933-021-01290-x

DO - 10.1186/s12933-021-01290-x

M3 - Article

C2 - 33962619

SN - 1475-2840

VL - 20

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

IS - 1

M1 - 102

ER -