Diabetes and Obesity Sex- and Gender-differences!

Transcription

1 Oskar Kokoschka 1908 Das Mädchen Li und ich Diabetes and Obesity Sex- and Gender-differences! Alexandra Kautzky Willer IGM, Berlin 2015

2 Global Diabetes-Epidemic Increase (%) in age-standardised diabetes - prevalence ( ) Diabetic women are diagnosed later and at higher BMI than men Increase of diabetes prevalence per decade: ~ 7% 8.3 (1980) 9.8% (2008) in males 7.5 (1980) 9.2% (2008) in females Tobias M, Lancet 2011

3 Excess Diabetes risk of subjects born during famines in Austria Males are more vulnerable More males Gestational Diabetes Importance of ensuring sufficient nutrition in prenatal and early stages of life! Thurner S, Kautzky-Willer A and Kasper D, PNAS 2013

4 Sex-Differences in Metabolism of Offspring of Parents with Diabetes (Scottish Family Health Study; Record-Linkage Study) Predictors of MetS in Female offspring: : Diabetic Mother (OR 1.8), BMI (OR 1.2), age (OR1.03) -female offspring of mothers with diabetes: higher glucose, higher body fat, lower HDL Cholesterol, higher rates of metabolic syndrome (MetS) even after adjusting for BMI Predictors of MetS in Male offspring: BMI (OR1.2), Body fat (OR1.1) Offspring of diabetic mothers (both sexes): higher blood pressure Offspring of diabetic parents (both sexes): higher BMI and body fat Body measurements, blood biochemistry and blood pressure measurements in offspring by parental group. Box-and-whiskers plots show median and IQR ( + within the box denotes mean value) for the OMD (white boxes), OFD (hatched boxes) and ONoPD (grey boxes) in males (left) and females (right); box-and whiskers for rest of cohort (RoC, i.e. all those without diabetes excluded from the F1-offspring groups, [black boxes] for males and females) are also shown for comparison. Graphs are shown for Waist (A), HDL-cholesterol (B), Glucose (C), Systolic-blood pressure (D), Diastolic-blood pressure (E), BMI (F) and Percent body-fat (G). Groups were compared by Kruskal-Wallis, with level of significance between the groups indicated (* P<0.05, **P<0.01, *** P<0.001, **** P<0.0001). Aldhous et al PLoS One

5 Birth weight is more strongly associated with type 2 diabetes in women than men Hazard ratios and 95% confidence intervals of adult type 2 diabetes according to birth weight Women Men Abbreviations: CI, Confidence Interval; kg, kilogram; The analysis was stratified by birth cohort Zimmermann et al Diabetes

6 BMI, physical activity and CLOCK Significant interaction between 3111T/C SNP (rs ) of the CLOCK gene and sex for overweight/obesity risk. Physical activity levels may act by modifying the association of the CLOCK gene polymorphism with overweight/obesity risk in elderly women. Galbete et al Chronobiol Int

7 Weight gain over 10 years and SNPs FTO in men and MMP2 in women are associated with weight gain over a 10- year follow-up period. Bouwman et al Genes Nutr

8 GWAS meta-analysis: BMI and SNPs BMI-associated loci 97 BMI-associated loci (P < 5 x 10-8 ) are identified accounting of 2.7% of BMI variation. Strong support for a role of the central nervous system in obesity susceptibility. Two loci, near SEC16B (P ) and ZFP64 (P ), showed evidence of heterogeneity between men and women. Both have stronger effects in women. Heterogeneity between sample sets and average imputation scores for BMI loci with P < SNP Chr. Position (bp) Nearest Genes P het for men vs. women Average imputation rs SEC16B 5,23E-05 0,988 rs ZFP64 9,05E-05 0,973 Locke et al Nature

9 Metabolic Characteristics Higher amounts of SAT in women and of VAT in men. In subjects with normal glucose tolerance (NGT) Women have better insulin sensitivity and insulin secretion adjusted for age and BMI compared to men. Women have lower fasting glucose levels and higher 2h levels (OGTT) Women have slower gastric emptying and prolonged gut glucose absorption compared to men Prediabetes & Diabetes: Women have higher rates of IGT Men have higher rates of IFG In diabetic patients the biological advantage of women dissapears. Kautzky-Willer A et al., Obesity 2012; Anderwald Ch et al., JCEM 2011; Faerch K et al., Diabetes Care 2015

10 GLP-1 Response to Oral Glucose Reduced in Prediabetes and T2DM Influenced by Sex Men Women Addition-Pro Study: Fasting and 2-h insulin concentrations were higher in men and women with prediabetes or type 2 diabetes compared with NGT individuals. In women, GLP-1 response (OGTT) was 25% lower in IFG&IGT and type 2 diabetes compared with the NGT group. In men, 120min GLP-1 concentrations were 16% lower in IFG&IGT and 13% lower in type 2 diabetes compared with NGT independent of age and obesity. Færch et al Diabetes

11 Risk factors of type 2 diabetes Age Ethnicity Family History (diabetic mothers!) Obesity (visceral!) Metabolic syndrome (Sex specific cut-offs: Waist Circumference, HDL-Cholesterol) Hyperglycemia during pregnancy Birth weight: LGA, SGA Fatty Liver Vascular Sex-specific: Disease Low Early SHBG menarche PCOS or high androgen levels in females Low socioeconomic status Prior Gestational Diabetes (7fold higher risk compared to normal Low glucose education tolerance during pregnancy) Smoking Erectile dysfuntion and/or low testosterone levels in males Low physical activity

12 Alcohol Consumption and the Risk of Type 2 Diabetes (Meta-analysis) Consumption among men showed no reduction in risk at any level of exposure, with decreases specific to women and present across a narrower range of exposure (0.61 g/day) [peak reduction of 34% at 31-37g/day] Knott, Bell, & Britton 2015 Diabetes Care

13 Night-work exposure and type 2 diabetes: ELSA-Brasil Among men, only after 20 years of exposure (solid line, change in curve pattern) a trend was observed for a positive association between night work and diabetes. Among women, in contrast, there was no specific cut-off value; the association between diabetes and years of exposure to night work increased in a linear fashion. Adjusted for confounders, including obesity Night work >20 years: Risk of diabetes: Women: OR: 1.4 Men: OR 1.06 Silva-Costa et al Scand J Work Environ Health

14 Diabetes Risk + Weight Reduction 3 years following Lifestyle Intervention Diabetes Risk Weight Loss Glechner 2015 Diabteologia

15 Lifestyle Interventions (6 years) Da Qing Study 23-year-follow-up All-cause mortality A 6-year lifestyle intervention programm for people with IGT can reduce incidence of CVD and allcause mortality and diabetes. Diabetes Incidence CVD mortality Li 2014 Lancet Endocrinology

16 Lifestyle Interventions Da Qing Study 23-year-follow-up Women Greater benefit in women! Men CVD Mortality All-cause Mortality Li 2014 Lancet Endocrinology

17 DIABETES: Relative risks and Sex Ratios for Core Comorbidities Klimek P, Kautzky-Willer A et al., PLOS Comp. Biol. 2015

18 University Course Gender Medicine Gender Medicine: Man and Woman in Focus Postgraduate University Course imparts specialist knowledge for individual and gender-specific health care (since September 2010) 4 Semesters 90 ECTS Starts again in Autumn 2017 Alexandra Kautzky-Willer, Gender Medicine Unit, Medical University of Vienna

19 Thank you for your attention!!!