The metabolic syndrome varies in prevalence among different populations. A common feature, however, is a steep increase in prevalence along with a decrease in glucose tolerance (1–2).
We have shown that 39% of adult type 1 diabetic patients have the metabolic syndrome (3), and similar data were recently reported from Italy (4). However, whether the metabolic syndrome observed in type 1 diabetes is the same as in nondiabetic and type 2 diabetic patients is unclear.
Both lifestyle (5–8) and hereditary factors (9) seem to be involved in the development of the metabolic syndrome in nondiabetic and type 2 diabetic subjects. The PPARγ (peroxisome proliferator-activated receptor γ) Pro12Ala polymorphism has been associated with type 2 diabetes, the Ala allele being associated with a lower risk (10), and with the metabolic syndrome in some (11–12) but not all (13) studies. However, whether lifestyle or genetic factors also play a role in the development and treatment of the metabolic syndrome in patients with type 1 diabetes is unknown.
Therefore, to further study the metabolic syndrome in type 1 diabetes, we investigated whether physical activity and/or the PPARγ Pro12Ala polymorphism are associated with metabolic syndrome in patients with type 1 diabetes in the Finnish Diabetic Nephropathy (FinnDiane) Study.
RESEARCH DESIGN AND METHODS—
Using a cross-sectional study design, 1,028 type 1 diabetic patients from the FinnDiane Study (3,14) with data on leisure-time physical activity (LTPA) and metabolic syndrome were studied. Patients with end-stage renal disease and/or cardiovascular events were excluded.
Metabolic syndrome was defined according to the NCEP/ATP III (National Cholesterol Education Program/Adult Treatment Panel III) criteria (15). LTPA (as MET h/week) was assessed by a validated 12-month questionnaire (16), and patients were grouped as sedentary, moderately active, or active as previously described (14). The PPARγ Pro12Ala (rs1801282) polymorphism was studied from 840 of the 1,028 patients using an ABI Prism 7900 Sequence Detection System (Applied Biosystems, Foster City, CA).
RESULTS—
The mean ± SD age was 36.4 ± 11.5 years, duration of diabetes 21.3 ± 11.7 years, A1C 8.4 ± 1.4%, BMI 25.0 ± 3.3 kg/m2, and 47% of patients were men. Median (interquartile range) LTPA was 19.7 (10.0–34.1) MET h/week. The prevalence of metabolic syndrome was 29.5% (ratio of men to women 27.8:31.0%, P = 0.269); 31.8% had the Ala-allele for PPARγ Pro12Ala (2.6% were homozygous). According to genotype, there were no differences in BMI, waist-to-hip ratio, lipid profile or, A1C (data not shown).
The prevalence of metabolic syndrome did not differ by genotype (Pro12Pro 30.4%, Pro12Ala 30.6%, Ala12Ala 36.4%; P = 0.836). LTPA in the presence versus absence of metabolic syndrome was 17.0 (8.6–31.6) vs. 20.8 (10.8–34.7) MET h/week (age-adjusted P = 0.038). Table 1 shows the prevalences of the metabolic syndrome and its individual components according to LTPA and PPARγ genotype.
Among patients reporting LTPA of low, moderate, or high intensity, 39.0, 28.3, and 23.2% (age-adjusted P = 0.008) had metabolic syndrome, respectively. Regarding frequency of LTPA, corresponding prevalences for <1, 1–2, or ≥3 sessions/week were 33.0, 29.9, and 27.7% (age-adjusted P = 0.325), respectively.
In a multiple logistic regression model, LTPA as a log-transformed continuous variable (odds ratio [OR] 0.73 [95% CI 0.58–0.92]) and laser-treated retinopathy (1.97 [1.19–3.27]) were independently associated with the metabolic syndrome. The model also included PPARγ Pro12Pro genotype (0.99 [0.62–1.58]), weekly doses (12 g/dose) of alcohol (1.26 [0.98–1.60]), male sex (0.98 [0.62–1.56]), age (1.01 [0.99–1.03]), low social class (1.09 [0.69–1.72]), smoking (0.76 [0.45–1.30]), and diabetic nephropathy (1.84 [0.92–3.68]).
CONCLUSIONS—
Low LTPA was associated with a higher prevalence of the metabolic syndrome, supporting our previous findings on LTPA and insulin sensitivity in type 1 diabetes (14). Due to the cross-sectional study design, LTPA could have been reduced by exercise-limiting factors associated with the metabolic syndrome. However, the likelihood of complication-derived physical activity bias was reduced by controlling for diabetes complications.
The PPARγ Pro12Ala polymorphism was not associated with the metabolic syndrome. Patients with the Ala allele, however, had a 2.4-fold higher prevalence of the metabolic syndrome when sedentary patients were compared with those who were physically active, while in patients with the Pro12Pro genotype, LTPA did not affect the prevalence of the metabolic syndrome. Of individual criteria, waist circumference seemed important for this genotype-dependent association, favoring a pivotal role of insulin sensitivity, the key factor in the metabolic syndrome (17).
Interestingly, the Ala allele has been associated with greater exercise-induced improvement of insulin sensitivity measures (18–19) in healthy individuals and reduction in fasting plasma glucose in type 2 diabetic patients (20). In the Finnish Diabetes Prevention Study, a paradoxical diabetogenic effect of the Ala allele in subjects with impaired glucose tolerance was eliminated by lifestyle intervention (21).
Based on our study and the findings of the Finnish Diabetes Prevention Study, the Ala allele might be viewed as not exclusively beneficial for insulin sensitivity and glucose homeostasis because the Ala allele, when combined with low physical activity, may on the contrary be detrimental. In our study, sedentary Ala carriers more frequently had metabolic syndrome than sedentary patients with Pro12Pro genotype. Thus, PPARγ Pro12Ala may be a true exercise-response gene variant working in both directions, promoting insulin sensitivity in those who are physically active while impeding sensitivity in sedentary subjects.
Proportion of type 1 diabetic patients with the metabolic syndrome and its individual components* according to level of LTPA and genotype for PPARγ Pro12Ala
| . | Sedentary . | Moderately active . | Active . | P† . | P‡ . |
|---|---|---|---|---|---|
| n | 254 | 588 | 186 | — | — |
| Metabolic syndrome (all) | 35.0 | 28.4 | 25.3 | 0.058 | 0.021 |
| Pro12Pro | 33.6 | 29.4 | 28.6 | 0.600 | 0.358 |
| Ala carrier | 43.8 | 29.6 | 18.2 | 0.015 | 0.004 |
| Individual components | — | — | — | — | — |
| Waist (all) | 21.7 | 14.6 | 11.8 | 0.009 | 0.004 |
| Pro12Pro | 19.1 | 14.2 | 12.4 | 0.266 | 0.121 |
| Ala carrier | 29.7 | 15.1 | 6.8 | 0.004 | 0.001 |
| Triglycerides (all) | 16.1 | 12.6 | 11.3 | 0.259 | 0.120 |
| Pro12Pro | 15.1 | 13.0 | 13.3 | 0.813 | — |
| Ala carrier | 15.6 | 9.4 | 2.3 | 0.070 | 0.021 |
| HDL-cholesterol (all) | 26.8 | 25.0 | 25.3 | 0.861 | — |
| Pro12Pro | 28.9 | 27.2 | 27.6 | 0.926 | — |
| Ala carrier | 31.3 | 24.5 | 27.3 | 0.586 | — |
| Hypertension (all) | 66.5 | 60.2 | 60.8 | 0.209 | — |
| Pro12Pro | 66.4 | 61.1 | 57.1 | 0.297 | 0.122 |
| Ala carrier | 73.4 | 59.1 | 65.9 | 0.125 | — |
| . | Sedentary . | Moderately active . | Active . | P† . | P‡ . |
|---|---|---|---|---|---|
| n | 254 | 588 | 186 | — | — |
| Metabolic syndrome (all) | 35.0 | 28.4 | 25.3 | 0.058 | 0.021 |
| Pro12Pro | 33.6 | 29.4 | 28.6 | 0.600 | 0.358 |
| Ala carrier | 43.8 | 29.6 | 18.2 | 0.015 | 0.004 |
| Individual components | — | — | — | — | — |
| Waist (all) | 21.7 | 14.6 | 11.8 | 0.009 | 0.004 |
| Pro12Pro | 19.1 | 14.2 | 12.4 | 0.266 | 0.121 |
| Ala carrier | 29.7 | 15.1 | 6.8 | 0.004 | 0.001 |
| Triglycerides (all) | 16.1 | 12.6 | 11.3 | 0.259 | 0.120 |
| Pro12Pro | 15.1 | 13.0 | 13.3 | 0.813 | — |
| Ala carrier | 15.6 | 9.4 | 2.3 | 0.070 | 0.021 |
| HDL-cholesterol (all) | 26.8 | 25.0 | 25.3 | 0.861 | — |
| Pro12Pro | 28.9 | 27.2 | 27.6 | 0.926 | — |
| Ala carrier | 31.3 | 24.5 | 27.3 | 0.586 | — |
| Hypertension (all) | 66.5 | 60.2 | 60.8 | 0.209 | — |
| Pro12Pro | 66.4 | 61.1 | 57.1 | 0.297 | 0.122 |
| Ala carrier | 73.4 | 59.1 | 65.9 | 0.125 | — |
Data are percentages unless otherwise indicated. Ala carriers: Pro12Ala or Ala12Ala genotype. Patients: all, n = 1028; Pro12Pro, n = 573; Ala carrier, n = 267.
According to the NCEP ATP III (National Cholesterol Education Program/Adult Treatment Panel III) criteria: waist circumference >102 cm (men), >88 cm (women); triglycerides ≥1.70 mmol/l; HDL cholesterol <1.00 mmol/l (men), <1.30 mmol/l (women); and blood pressure ≥130/85 mmHg or antihypertensive medication. All patients fulfilled the criteria for fasting blood glucose ≥6.11 mmol/l. A minimum of three criteria were requested for diagnosis of the metabolic syndrome.
χ2 test;
χ2 test for trend.
Article Information
This study was supported by the Folkhälsan Research Foundation, Samfundet Folkhälsan, Wilhelm och Else Stockmann Foundation, Sigrid Juselius Foundation, Waldemar von Frenckell Foundation, Liv och Hälsa Foundation, the Academy of Finland (no. 214335), and the European Commission (QLG2-CT-2001-01669). The assistance of Anna Sandelin, Sinikka Lindh, and Susanne Ström is gratefully acknowledged. Finally, we acknowledge physicians and nurses at each study center, presented in an online appendix (available at http://dx.doi.org/10.2337/dc06-2467).
References
Published ahead of print at http://care.diabetesjournals.org on 10 March 2007. DOI: 10.2337/dc06-2467.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc06-2467.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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