The purpose of the present study was to examine 10-year cardiovascular morbidity and mortality in patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic ...control subjects and to evaluate the effects of general risk factors, plasma insulin, urinary albumin excretion, lipoprotein abnormalities characteristic of Type 2 diabetes and the degree of hyperglycaemia in diabetic patients on cardiovascular mortality. Furthermore, the extent to which the above-mentioned factors could contribute to the excessive cardiovascular mortality observed in diabetic patients was examined. In the years 1979-1981, altogether 133 (70 men, 63 women) newly-diagnosed patients with Type 2 diabetes and 144 (62 men, 82 women) non-diabetic control subjects aged 45-64 years were studied. Both groups were re-examined in the years 1985-1986 and 1991-1992. The impact of different factors on cardiovascular mortality was examined by univariate analyses after adjustment for age and sex and by multiple logistic regression analyses. The age-standardized total and cardiovascular mortality rates were substantially higher in diabetic men (17.8 and 15.0%, total and cardiovascular mortality, respectively p = 0.06 and NS) and women (18.5 and 16.6%, p < 0.01 for both) than in non-diabetic control men (5.2% both total and cardiovascular mortality) and women (4.2 and 2.2%). Cardiovascular mortality was not related to the treatment modality (diet, oral drugs, insulin) at 5 years from diagnosis. Use of diuretics, beta-blocking agents or their combination at baseline did not make a significant contribution to cardiovascular mortality either. In multiple logistic regression analysis on diabetic patients, age, LDL triglycerides, smoking, blood glucose and ischaemic ECG at baseline had independent associations with cardiovascular mortality. Interestingly, urinary albumin excretion rate measured at 5-year examination also predicted 10-year cardiovascular mortality after adjustment for the effects of major risk factors including lipoprotein abnormalities, but its predictive power reduced to a nonsignificant level when the effect of plasma glucose was taken into account. The relative risk of cardiovascular mortality associated with diabetes was 8.2 after allowing for age alone, but it declined to 3.7 when all contributing factors from the baseline examination (except blood glucose) were taken into account. In conclusion, the present results indicate that LDL triglycerides and/or other changes in lipoprotein composition characteristic of Type 2 diabetes and manifesting as elevated serum triglycerides are atherogenic and they strongly predict increased cardiovascular mortality.
Diabet. Med. 29, e126–e132 (2012)
Aims To assess the effect of lifestyle intervention on depressive symptoms during a 36‐month randomized clinical trial designed to prevent Type 2 diabetes.
Methods ...A total of 522 middle‐aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants.
Results On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (−1.99 to −0.19) scores in the intervention group and 0.75 ± 4.47 (−1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R2 = 0.209, P < 0.001).
Conclusions Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one’s lifestyle and behaviour is associated with beneficial changes in mood.
Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFκB) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in ...mediating insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NFκB activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB. Methods We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n = 24) or control group (n = 10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT. Results In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p < 0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group. Conclusions/interpretation These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome. Trial registration: ClinicalTrials.gov NCT 00621205
Aim
To examine changes in glucose metabolism (fasting and 2‐h glucose) during follow‐up in people with impaired fasting glucose in comparison with changes in people with isolated impaired glucose ...tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening‐detected Type 2 diabetes at baseline, among those who participated in a diabetes prevention programme conducted in Finland.
Methods
A total of 10 149 people at high risk of Type 2 diabetes took part in baseline examination. Of 5351 individuals with follow‐up ≥ 9 months, 1727 had impaired glucose metabolism at baseline and completed at least one lifestyle intervention visit. Most of them (94.6%) were overweight/ obese.
Results
Fasting glucose decreased during follow‐up among overweight/obese people in the combined impaired fasting glucose and impaired glucose tolerance group (P = 0.044), as did 2‐h glucose in people in the isolated impaired glucose tolerance group (P = 0.0014) after adjustment for age, sex, medication and weight at baseline, follow‐up time and changes in weight, physical activity and diet. When comparing changes in glucose metabolism among people with different degrees of glucose metabolism impairment, fasting glucose concentration was found to have increased in those with isolated impaired glucose tolerance (0.12 mmol/l, 95% Cl 0.05 to 0.19) and it decreased to a greater extent in those with screening‐detected Type 2 diabetes (−0.54 mmol/l, 95% Cl −0.69 to −0.39) compared with those with impaired fasting glucose (−0.21 mmol/l, 95% Cl −0.27 to −0.15). Furthermore, 2‐h glucose concentration decreased in the isolated impaired glucose tolerance group (−0.82 mmol/l, 95% Cl −1.04 to −0.60), in the combined impaired fasting glucose and impaired glucose tolerance group (−0.82 mmol/l, 95% Cl −1.07 to −0.58) and in the screening‐detected Type 2 diabetes group (−1.52, 95% Cl −1.96 to −1.08) compared with those in the impaired fasting glucose group (0.26 mmol/l, 95% Cl 0.10 to 0.43). Results were statistically significant even after adjustment for covariates (P < 0.001 in all models).
Conclusions
Changes in glucose metabolism differ in people with impaired fasting glucose from those in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening‐detected Type 2 diabetes.
What's new?
Results from implementation trials of programmes for the prevention of Type 2 diabetes are scarce in primary healthcare settings. This study provides new information on changes in glucose metabolism in people with impaired fasting glucose and other categories of impaired glucose metabolism, among participants in a lifestyle intervention programme in primary healthcare settings in Finland.
The results suggest that changes in glucose metabolism differ in people with impaired fasting glucose from those in people with other categories of impaired glucose metabolism.
Despite the potential importance of favorable changes in the lipid profile produced by aerobic exercise, training-induced lipid profile changes in atherosclerosis-prone type 1 diabetes mellitus (DM) ...have not heretofore been adequately addressed.
We assessed the effect of a 12- to 16-wk aerobic exercise program on cardiorespiratory fitness and the lipid profile in young men with type 1 DM. Generally active men aged 20-40 yr with type 1 DM (N = 56) were randomized into training (N = 28) and control (untrained, N = 28) groups after baseline measurements. Training consisted of 30-60 min moderate-intensity running 3-5 times a week for 12-16 wk.
For the 42 men finishing the study, peak oxygen consumption (VO2 peak) increased significantly only in the trained group. Total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B decreased and the high-density lipoprotein (HDL)/apo A-I ratio increased in the trained group. HDL and apo A-I increased in both groups. The exercise program brought about improvements in the HDL/LDL and apo A-I/apo B ratios and apo B and triglyceride levels when comparing the relative (%) changes in the trained versus control group. In the trained group, men with HDL/LDL ratios below the group median at baseline showed even more favorable changes in their lipid profile than those with higher initial HDL/LDL ratios. Body mass index, percent body fat and hemoglobin A1c did not change during the training period in either group.
Endurance training improved the lipid profile in already physically active type 1 diabetic men, independently of effects on body composition or glycemic control. The most favorable changes were in patients with low baseline HDL/LDL ratios, likely the group with the greatest benefit to be gained by such changes.
Background
We evaluated the benefit of using combined genetic risk score (GRS) of known single nucleotide polymorphisms (SNPs) for body mass index (BMI) and waist/hip ratio (WHR) in the prediction of ...weight loss and weight regain after obesity surgery.
Methods
A total of 163 consecutive morbidly obese individuals undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in a single bariatric center in Finland were recruited. Fasting blood samples were drawn after 12 h of fasting before and 1 year after bariatric operation. Data for weight regain and medication were collected with a questionnaire after 3.1 ± 2.7 years (mean ± SD) follow-up. Nonalcoholic steatohepatitis (NASH) was diagnosed with liver histology. Twenty BMI- and 13 WHR-related SNPs were genotyped. Linear regression was used to identify factors predicting weight loss and weight regain.
Results
Lower baseline BMI predicted greater decline in BMI (
p
= 0.0005) and excess weight loss (EWL) (
p
= 0.009). In the multiple linear regression analysis age and BMI, explained the variance of EWL during the first year while GRS, sex, fasting plasma glucose, serum insulin and NASH diagnosis did not have any effect. None of the baseline clinical variables explained BMI regain. The combined GRS did not associate with weight or BMI at baseline, with 1-year changes or with weight regain between 1 year and an average of 3.1 years follow-up.
Conclusions
In our study, we found that the genotype risk score does not predict weight loss after obesity surgery while lower baseline BMI predicted the greater weight loss.
Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a
15-year follow-up from the time of diagnosis.
L Niskanen ,
A Turpeinen ,
I ...Penttilä and
M I Uusitupa
Department of Clinical Nutrition, University of Kuopio, Finland. leo.niskanen@kuh.fi
Abstract
OBJECTIVE: We studied the 15-year cardiovascular mortality and morbidity of newly diagnosed patients with type 2 diabetes
and of nondiabetic control subjects and the predictors of cardiovascular mortality in diabetic patients. RESEARCH DESIGN AND
METHODS: We performed a 15-year prospective study of 133 middle-aged patients with newly diagnosed type 2 diabetes and 144
control subjects. Cardiovascular risk factors were assessed in both groups at baseline and after 5 and 10 years. RESULTS:
Total mortality was markedly higher in patients with type 2 diabetes (total: 44.3 vs. 12.9% for men, age-adjusted odds ratio
OR 5.0, P < 0.001; 44.4 vs. 11.0% for women, OR 5.2, P < 0.001), which was due to increased cardiovascular mortality (ORs
for men and women: 6.2 and 11.2, respectively, P < 0.001 for both). The incidences of fatal and nonfatal myocardial infarction
and stroke were likewise higher in diabetic patients. In univariate analyses and various multiple logistic regression analyses,
hyperglycemia was a constant predictor of cardiovascular mortality assessed at the time of diagnosis or at 5- or 10-year examinations.
Moreover, lipoprotein abnormalities characteristic of type 2 diabetes (low HDL cholesterol, high LDL triglycerides or apolipoprotein
B levels, and low LDL cholesterol/apolipoprotein B ratio as a marker for LDL size) were predictive of cardiovascular death
in these analyses. CONCLUSIONS: This long-term study of a well-characterized group of newly diagnosed patients strengthens
the view that the prognosis in middle-aged subjects is markedly impaired and that both hyperglycemia and compositional lipoprotein
abnormalities are predictors of cardiovascular mortality in patients with type 2 diabetes.
OBJECTIVE Recent research suggests that oats do not harm intestinal villi in adults with coeliac disease. As the immunological effects of oats have not been examined in detail, it was decided to ...compare the immunological responses of a gluten free diet including oats with those of a conventional gluten free diet. DESIGN A randomised controlled intervention study over 6–12 months. SUBJECTS Forty adults with newly diagnosed coeliac disease and 52 with coeliac disease in remission were examined. INTERVENTION The effects of a gluten free diet including oats and a conventional gluten free diet were compared. MAIN OUTCOME MEASURES Serum levels of gliadin and reticulin antibodies as well as numbers of intraepithelial lymphocytes (IELs) in intestinal mucosa were examined before and after the intervention. RESULTS The rate of disappearance of gliadin and reticulin antibodies did not differ between the diet groups in patients with newly diagnosed coeliac disease. Oats also had no effect on gliadin or reticulin antibody levels in the patients with remission. The number of IELs decreased similarly regardless of the diet of newly diagnosed patients, and no increase in the number of IELs was found in the patients in remission with or without oats. CONCLUSIONS These results strengthen the view that adult patients with coeliac disease can consume moderate amounts of oats without adverse immunological effects.
Methods: We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m2) and ...waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. Results: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. Conclusions: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.
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