Objective
To obtain evidence of the effects of metformin and statins on the incidence of ovarian cancer in women with type 2 diabetes (T2D).
Design
A retrospective cohort study and nested ...case–control study.
Setting
The data were obtained from a diabetes database (FinDM) combining information from several nationwide registers.
Population
A cohort of 137 643 women over 40 years old and diagnosed with T2D during 1996–2011 in Finland.
Methods
In full cohort analysis Poisson regression was used to estimate the hazard ratios (HR) in relation to ever use of metformin, insulin other oral anti‐diabetic medication or statins. In the nested case–control analysis 20 controls were matched to each case of ovarian cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different medications. The estimates were adjusted for age and duration of T2D.
Main outcome measure
Incidence of ovarian cancer.
Results
In all, 303 women were diagnosed with ovarian cancer during the follow up. Compared with other forms of oral anti‐diabetic medication, metformin (HR 1.02, 95% CI: 0.72–1.45) was not found to be associated with the incidence of ovarian cancer. Neither was there evidence for statins to affect the incidence (HR 0.99, 95% CI: 0.78–1.25). In nested case–control analysis the results were essentially similar.
Conclusions
No evidence of an association between the use of metformin or statins and the incidence of ovarian cancer in women with T2D was found.
Tweetable
No evidence found for metformin or statins reducing the incidence of ovarian cancer.
Tweetable
No evidence found for metformin or statins reducing the incidence of ovarian cancer.
Aims/hypothesis
This study aimed to determine whether lifestyle intervention lasting for 4 years affected diabetes incidence, body weight, glycaemia or lifestyle over 13 years among individuals at ...high risk of type 2 diabetes.
Methods
Overweight, middle-aged men (
n
= 172) and women (
n
= 350) with impaired glucose tolerance were randomised in 1993–1998 to an intensive lifestyle intervention group (
n
= 265), aiming at weight reduction, dietary modification and increased physical activity, or to a control group (
n
= 257) that received general lifestyle information. The primary outcome was a diagnosis of diabetes based on annual OGTTs. Secondary outcomes included changes in body weight, glycaemia, physical activity and diet. After active intervention (median 4 years, range 1–6 years), participants still free of diabetes and willing to continue their participation (200 in the intervention group and 166 in the control group) were further followed until diabetes diagnosis, dropout or the end of 2009, with a median total follow-up of 9 years and a time span of 13 years from baseline.
Results
During the total follow-up the adjusted HR for diabetes (intervention group vs control group) was 0.614 (95% CI 0.478, 0.789;
p
< 0.001). The corresponding HR during the post-intervention follow-up was 0.672 (95% CI 0.477, 0.947;
p
= 0.023). The former intervention group participants sustained lower absolute levels of body weight, fasting and 2 h plasma glucose and a healthier diet. Adherence to lifestyle changes during the intervention period predicted greater risk reduction during the total follow-up.
Conclusions/interpretation
Lifestyle intervention in people at high risk of type 2 diabetes induces sustaining lifestyle change and results in long-term prevention of progression to type 2 diabetes.
Trial registration
ClinicalTrials.gov NCT00518167
Funding
The DPS study has been financially supported by the Academy of Finland (128315, 129330), Ministry of Education, Novo Nordisk Foundation, Yrjö Jahnsson Foundation, Juho Vainio Foundation, Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, Unilever, and Competitive Research Funding from Tampere, Kuopio and Oulu University Hospitals. The study sponsors had no role in the design and conduct of the study; the collection, analysis and interpretation of the data; or the preparation, review or approval of the manuscript.
Diabet. Med. 28, 699–704 (2011)
Aims The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance ...and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort.
Methods Two hundred and sixty‐eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow‐up, were studied for cardiovascular autonomic neuropathy. At the second annual follow‐up visit after the end of lifestyle intervention, we performed deep‐breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA1c, serum lipids and blood pressure were carried out.
Results Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight, waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P < 0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA1c. Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women.
Conclusions Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy.
The incidence of type 2 diabetes mellitus is increasing worldwide. Type 2 diabetes results from the interaction between a genetic predisposition and behavioral and environmental risk factors.
1
...Although the genetic basis of type 2 diabetes has yet to be identified, there is strong evidence that such modifiable risk factors as obesity and physical inactivity are the main nongenetic determinants of the disease.
2
–
9
Impaired glucose tolerance is an intermediate category between normal glucose tolerance and overt diabetes,
10
,
11
and it can be identified by an oral glucose-tolerance test. Subjects with impaired glucose tolerance have an increased risk of type 2 . . .
Aims/hypothesis Subclinical inflammation confers an increased risk of type 2 diabetes, cardiovascular disease, neurodegenerative disorders and other age-related chronic diseases. Physical activity ...and diet can attenuate systemic immune activation, but it is not known which individual components of a comprehensive lifestyle intervention are most effective in targeting subclinical inflammation. Methods We used data from the baseline examination and the 1 year follow-up of a subsample of 406 of 522 participants of the Finnish Diabetes Prevention Study (DPS) to estimate the effect of individual components of lifestyle intervention on C-reactive protein (CRP) and IL-6 levels, which represent the best characterised proinflammatory risk factors for type 2 diabetes. Changes in metabolic markers, dietary patterns and exercise were analysed to determine which were most strongly associated with the anti-inflammatory effect of lifestyle changes. Results Lifestyle intervention reduced circulating levels of CRP (p < 0.001) and IL-6 (p = 0.060). Increases in fibre intake and moderate to vigorous leisure time physical activity (LTPA), but not total LTPA, predicted decreases in CRP and/or IL-6 and remained associated even after adjustment for baseline BMI or changes in BMI during the first year of the study. Changes in carbohydrate or fat intake were either weakly or not linked to reductions in CRP and IL-6. Conclusions/interpretation The present study assessed the individual effects of dietary and physical activity measures on low-grade inflammation in individuals at high cardiometabolic risk. Our results underline the importance of moderate to vigorous LTPA and a diet rich in natural fibre, and this should be emphasised in lifestyle recommendations. Trial registration: ClinicalTrials.gov NCT00518167 Funding: The study was funded by the European Foundation for the Study of Diabetes, the German Federal Ministry of Health, the Ministry of Innovation, Science, Research and Technology of the State of North Rhine-Westphalia, the German Diabetes Foundation (Deutsche Diabetes-Stiftung), the Department of Internal Medicine II--Cardiology at the University of Ulm, the Academy of Finland, the Juho Vainio Foundation, the Finnish Ministry of Education, the Novo Nordisk Foundation, the Yrjö Jahnsson Foundation, the Finnish Diabetes Research Foundation and EVO funds from Tampere and Kuopio University Hospital.
To obtain further evidence of the association between metformin or other types of antidiabetic medication (ADM) and mortality from endometrial cancer (EC) and other causes of death in patients with ...endometrioid EC and type 2 diabetes (T2D).
A retrospective cohort of women with existing T2D and diagnosed with endometrioid EC from 1998 to 2011, obtained from a nationwide diabetes database (FinDM), were included in the study. Cumulative mortality from EC and that from other causes was described by using the Aalen-Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models, and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were estimated in relation to the use of different forms of ADM during the three-year period preceding EC diagnosis.
From the FinDM cohort we identified 1215 women diagnosed with endometrioid EC, of whom 19% were metformin users, 12% were users of other types of oral antidiabetic medication, 25% used other types of oral antidiabetic medication plus metformin, 26% used insulin and 14% had no antidiabetic medication. Mortality from EC was not found to be different in women using metformin (HR 0.89, 95% Cl 0.52–1.54) but mortality from other causes was lower (HR 0.52, 95% Cl 0.31–0.88) compared with women using other types of oral ADM.
Our findings are inconclusive as to the possible effect of metformin on the prognosis of endometrioid EC in women with T2D. However, use of metformin may reduce mortality from other causes.
•Our findings were inconclusive regarding the possible effect of metformin on the prognosis of endometrioid EC in women with T2D.•Mortality from other causes was lower in metformin users compared to those with other forms of oral antidiabetic medication.•Our results on non-EC mortality are consistent with other studies on metformin use and mortality.
Diabet. Med. 28, 36–42 (2011)
Aims We analysed the Finnish Diabetes Prevention Study data in order to evaluate how the new HbA1c‐based criterion compares with the oral glucose tolerance test in ...diagnosing Type 2 diabetes among high‐risk individuals during a prospective average follow‐up of 4 years.
Methods In the Diabetes Prevention Study, 172 men and 350 women who were overweight and had impaired glucose tolerance at baseline were randomized into an intensive lifestyle intervention or a control group. The oral glucose tolerance test and HbA1c measurements were performed annually until the diagnosis of diabetes using the World Health Organization 1985 criteria.
Results The sensitivity of the HbA1c≥ 6.5% (≥ 48 mmol/mol) as a diagnostic criterion for Type 2 diabetes was 35% (95% CI 24%, 47%) in women and 47% (95% CI 31%, 64%) in men compared with diagnosis based on two consecutive oral glucose tolerance tests. The corresponding sensitivities for HbA1c≥ 6.0% (≥ 42 mmol/mol) were 67% (95% CI 55%, 77%) and 68% (95% CI 51%, 82%). The participants with HbA1c≥ 6.5% (≥ 48 mmol/mol) and diabetes based on the oral glucose tolerance test were more obese and had higher fasting glucose and 2‐h glucose concentrations than those who had a diabetic oral glucose tolerance test but HbA1c < 6.5% (< 48 mmol/mol). There were no differences in the predictive performance of baseline fasting glucose, oral glucose tolerance test and HbA1c.
Conclusions Of those with diabetes diagnosis based on two oral glucose tolerance tests during the Diabetes Prevention Study follow‐up, 60% would have remained undiagnosed if diagnosis had been based on HbA1c≥ 6.5% (≥ 48 mmol/mol) criterion.
OBJECTIVES: To investigate associations of long-term nutrient intake, physical activity and obesity with later cognitive function among the participants in the Finnish Diabetes Prevention Study, in ...which a lifestyle intervention was successful in diabetes prevention. DESIGN: An active lifestyle intervention phase during middle age (mean duration 4 years) and extended follow-up (additional 9 years) with annual lifestyle measurements, followed by an ancillary cognition assessment. SETTING: 5 research centers in Finland. PARTICIPANTS: Of the 522 middle-aged, overweight participants with impaired glucose tolerance recruited to the study, 364 (70%) participated in the cognition assessment (mean age 68 years). MEASUREMENTS: A cognitive assessment was executed with the CERAD test battery and the Trail Making Test A on average 13 years after baseline. Lifestyle measurements included annual clinical measurements, food records, and exercise questionnaires during both the intervention and follow-up phase. RESULTS: Lower intake of total fat (p=0.021) and saturated fatty acids (p=0.010), and frequent physical activity (p=0.040) during the whole study period were associated with better cognitive performance. Higher BMI (p=0.012) and waist circumference (p=0.012) were also associated with worse performance, but weight reduction prior to the cognition assessment predicted worse performance as well (decrease vs. increase, p=0.008 for BMI and p=0.002 for waist). CONCLUSIONS: Long-term dietary fat intake, BMI, and waist circumference have an inverse association with cognitive function in later life among people with IGT. However, decreases in BMI and waist prior to cognitive assessment are associated with worse cognitive performance, which could be explained by reverse causality.
Abstract Background and aims We examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention ...Study (DPS). We also explored a possible interaction of ABCG8 rs4299376 on sterol levels and lifestyle intervention. Methods and results We conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994–2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had β-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in β-sitosterol and campesterol: 0.76 0.63–0.92, and 0.81 0.67–0.99, respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 1.13–1.62). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on β-sitosterol ( p = 0.001) and campesterol ( p = 0.004) levels during the follow-up. Conclusions Markers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.
Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics ...approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of β-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
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