Fasting Serum Triglycerides Predict New Onset Diabetes Mellitus Independent of Physical Fitness

Transcription

1 Fasting Serum Triglycerides Predict New Onset Diabetes Mellitus Independent of Physical Fitness A 35 year follow-up of apparently healthy men Per Torger Skretteberg, MD (1), Anette Nordeide Grytten (2), Kathrine Gjertsen (2), Irene Grundvold, MD (1), Sverre E. Kjeldsen, MD PhD (1,2), Jan Erikssen, MD PhD (2), Knut Liestøl, PhD (3), Gunnar Erikssen, MD PhD (4), Terje R. Pedersen, MD PhD (2,5), Johan Bodegard, MD PhD (1). 1. Department of Cardiology, Oslo University Hospital, Ullevaal 2. University of Oslo, Faculty of Medicine 3. Department of Informatics, University of Oslo 4. Department of Cardiology, Oslo University Hospital, Rikshospitalet 5. Center of Preventive Medicine, Oslo University Hospital, Ullevaal UNIVERSITY OF OSLO FACULTY OF MEDICINE NORWEGIAN HEALTH ASSOCIATION

2 Disclosures The Oslo Ischemia Study group has received an unrestricted grant of euro Pronova BioPharma Norge AS in The first author has received travel support from Pronova BioPharma Norge AS. SE Kjeldsen receives "ad hoc honoraria for lectures from Novartis, AstraZeneca, Bayer, Boehringer-Ingelheim, Menarini, Merck, Sankyo, Sanofi, Servier and Takeda. L Mellbin has received research support from the The Swedish Heart- Lung Foundation, The Swedish Society of Cardiology, MSD Sweden and speakers honorarium from MSD Sweden, Sanofi Aventis Sweden, Novartis Europe Bayer- Schering Europe D.A.Fraser has a full-time position at Pronova Biopharma Norge AS TR Pedersen has received research support, speaker and consulting honoraria and travel support from Merck, and speaker honoraria from Pfizer, AstraZeneca and Novartis. J Bodegard also holds a full time position as epidemiologist in AstraZeneca The other authors have no disclosures

3 Background Fasting serum triglycerides have been suggested to predict new onset diabetes mellitus 1, 2 High levels of physical fitness are associated with reduced risk of new onset diabetes mellitus 3 Physical activity and increased physical fitness improve insulin sensitivity, reduce visceral body fat, and thereby influence triglycerides and other predictors of diabetes 4,5 1. Perry, IJ. Et al., BMJ 1995;310: Josepha, J. et al., Eur J Epidemiol 2011;26: Lynch, J et al., Arch Int Med 1996;156: Henriksen, EJ et al., J Appl Physiol 2002;93: Janiszewski, PM et al., Appl Physiol Nutr Metab 2007;32:

4 Background Whether triglycerides predict new onset diabetes in healthy middle-aged men remains elusive The impact of physical fitness on the predictive ability of triglycerides for new onset diabetes has not been studied

5 Objectives 1. To test the hypothesis that fasting serum triglycerides predict new onset diabetes in healthy middle-aged men 2. To test the impact of physical fitness on the prognostic ability of triglycerides for new onset diabetes

6 Study Population at Baseline Fasting serum triglycerides and physical fitness were measured in 1962 men aged years in Apparently healthy and free from known or suspected diabetes mellitus, heart disease, treated hypertension, malignancy and other serious disease Fasting blood glucose <6.1 mmol/l

7 Measurements at Baseline Fasting serum triglycerides: Fluorimetric method Fasting blood glucose (venous): Enzymatic method Physical fitness: Electrically braked bicycle with start load of 100W, increased by 50W every 6 th minute Symptom-limited Physical fitness defined as total work divided by body weight (kj/kg)

8 Diagnosis of Diabetes Mellitus Data from clinical examinations and hospital records Fasting blood glucose >7.8 mmol/l Glucosuria Blood glucose lowering drugs Risk profile, age at onset and clinical information including drugs indicated that most cases were type 2 diabetes

9 Statistics Kendall rank test to assess correlation (trend) between triglyceride levels and baseline data Cox proportional hazard analyses to study the risk association between triglycerides and new onset diabetes Main model adjusted for age, fasting blood glucose, body mass index and family history of maternal diabetes Additional adjustment for physical fitness to assess its impact on the prognostic ability of triglycerides

10 Baseline Characteristics Triglyceride Tertiles (T1-T3) T1 ( mmol/l) n=677 T2 ( mmol/l) n=630 T3 ( mmol/l) n=655 P-value (trend) Age, years (SD) 49.6 (5.5) 50.0 (5.5) 49.8 (5.5) ns BMI, kg/m 2 (SD) 23.6 (2.4) 24.5 (2.5) 25.6 (2.9) < Current smoker, n (%) 255 (37.7) 286 (45.4) 315 (48.1) Systolic BP, mmhg (SD) (16.8) (17.3) (17.8) < Total cholesterol, mmol/l (SD) 6.09 (1.01) 6.73 (1.05) 7.15 (1.23) < Fasting TG, mmol/l (SD) 0.78 (0.14) 1.17 (0.12) 2.00 (0.80) na Fasting blood glucose, mmol/l (SD) 4.35 (0.46) 4.43 (0.49) 4.49 (0.51) < Physical fitness, kj/kg (SD) 2.16 (0.89) 1.93 (0.77) 1.70 (0.62) < Maternal diabetes, n (%) 42 (6.2) 42 (6.7) 57 (8.7) ns(0.08)

11 Number of men Crude Incidence of New Onset Diabetes during Median Follow-up of 30.1 Years Triglyceride Tertiles (T1-T3) T1 ( mmol/l) T2 ( mmol/l) T3 ( mmol/l)

12 Men free from diabetes Survival free from New Onset Diabetes Triglyceride Tertiles (T1-T3) T1 T2 T3 T1 ( mmol/l) T2 ( mmol/l) T3 ( mmol/l) Observation time (Years)

13 Predictors of New Onset Diabetes Univariate Analysis: Ranked According to Chi Square Hazard Ratio (HR) per 1 SD Increase HR 95 % CI P-value Chi Square Fasting blood glucose (mmol/l) < Body mass index (kg/m 2 ) < Physical fitness (kj/kg) < Log serum triglycerides < Systolic blood pressure (mmhg) < Maternal diabetes (yes/no) < Age (years) Total cholesterol (mmol/l) Current smoker (yes/no)

14 Predictors of New Onset Diabetes Multivariate Analysis: Ranked According to Chi Square Hazard Ratio (HR) per 1 SD Increase HR 95 % CI P-value Chi Square Fasting blood glucose (mmol/l) < Body mass index (kg/m 2 ) < Maternal diabetes (yes/no) < Physical fitness (kj/kg) Log serum triglycerides Age (years) * 1.1 * Significant without physical fitness in the model

15 Relative Risk of New Onset Diabetes Triglyceride Tertiles (T1-T3) T1 ( mmol/l) n=677 T2 ( mmol/l) n=630 T3 ( mmol/l) n=655 Age adjusted ( ) 3.27 ( ) Multiple adjusted* without physical fitness ( ) 1.90 ( ) Multiple adjusted* with physical fitness ( ) 1.73 ( ) *Adjusted for age, body mass index, fasting blood glucose and maternal diabetes

16 We tested: Summary The prognostic ability of fasting serum triglycerides for risk of new onset diabetes mellitus in 1962 healthy middle-aged men followed up to 35 years The prognostic ability of fasting serum triglycerides for risk of new onset diabetes mellitus in middle-aged men when adjusting for physical fitness Fasting blood glucose and body mass index were the strongest predictors of diabetes The highest triglyceride tertile almost doubled the risk of new onset diabetes compared to the lowest and was highly significant even when adjusted for physical fitness (p< )

17 Conclusions Fasting serum triglyceride level is a significant long-term predictor of new onset diabetes mellitus in healthy middle-aged men Fasting serum triglyceride level is a significant long-term predictor of new onset diabetes mellitus in healthy middle-aged men even when adjusted for physical fitness Fasting serum triglycerides should be considered when estimating risk of diabetes irrespective of the level of physical fitness

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