To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives.
In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained.
We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers.
Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.
High cereal fibre intake is associated with reduced risk for type 2 diabetes, but wheat fibre had little or no effect on glycaemic control or oral glucose tolerance in clinical trials lasting 4-12 weeks. To explain this discrepancy, we hypothesised that colonic adaptation to increased wheat fibre intake takes many months but eventually results in increased SCFA production and glucagon-like peptide-1 (GLP-1) secretion. Thus, the primary objective was to determine the time-course of the effects of increased wheat fibre intake on plasma acetate, butyrate and GLP-1 concentrations in hyperinsulinaemic human subjects over 1 year. Subjects with fasting plasma insulin >or= 40 pmol/l were randomly assigned by computer to receive either a high-wheat fibre cereal (fibre group; 24 g fibre/d; twenty assigned; six dropped out, fourteen included) or a low-fibre cereal (control group; twenty assigned; six dropped-out, fourteen included) daily for 1 year. Acetate, butyrate and GLP-1 were measured during 8 h metabolic profiles performed every 3 months. There were no differences in body weight in the fibre group compared with the control group. After 9 months baseline-adjusted mean 8 h acetate and butyrate concentrations were higher on the high-fibre than the control cereal (P
Several studies have shown that insulin action deteriorates with age, possibly mediated through accumulation of abdominal fat. We determined peripheral insulin action in elderly and younger men who had participated in a large population study (the Tromsø Study). To 15 elderly participants aged 71 to 77 years, we individually matched 15 younger participants aged 31 to 33 years (Y1) by body mass index (BMI). A second young group (Y2) comprised 15 participants also aged 31 to 33 years, but with BMI representative of this age group in the population study. All underwent hyperinsulinemic euglycemic clamps (0.4 mU/kg/min), oral glucose tolerance tests, and determinations of Vo2max. Insulin sensitivity index (ISI=glucose disposal per kg fat-free mass [FFM] divided by steady-state insulin concentration) did not differ between the elderly and Y1, but was higher in Y2 (0.10+/-0.01, 0.12+/-0.01, and 0.17+/-0.02, P=.0011 by analysis of variance [ANOVA]). Adjustment by waist circumferences (analysis of covariance [ANCOVA]) abolished this difference. In univariate analysis of pooled data, ISI correlated negatively to body fat indices, serum triglycerides, and free fatty acids (FFA), and positively to Vo2max. In multiple regression analysis, waist circumference and triglycerides were the only independent predictors of insulin sensitivity, whereas age had no impact. The results confirm that the decline in insulin action seen in elderly people is related to increased abdominal fat rather than aging per se.
The relationship between non-esterified fatty acids (NEFA) in serum and heart muscle was examined in 15 patients who died of myocardial infarction (MI) and seven people who died suddenly in accidents. There was no correlation between NEFA levels of serum and non-infarcted cardiac muscle in patients with fatal MI. No significant difference was encountered in cardiac NEFA content between patients with fatal MI and people who died in accidents. The phospholipid (PL) content was significantly lower in patients with fatal MI than observed in people who died in accidents. The arachidonic acid (20:4 (n-6)) concentration of serum NEFA was significantly lower in patients with fatal MI compared to normal subjects. The cardiac NEFA and PL in patients with fatal MI contained significantly lower percentage levels of arachidonic acid compared to people who died in accidents. The results indicate that the death of the MI patients was not accompanied by elevated cardiac NEFA levels.
OBJECTIVE: To assess age-related changes in stimulated plasma C-peptide in a population-based sample of adults. DESIGN: Cross-sectional study. SETTING: Wadena, Minnesota, a city of 4,699 residents (1980 census) in west central Minnesota, approximately 150 miles from Minneapolis/St. Paul. STUDY SUBJECTS: 344 non-diabetic subjects (NDDG standards) from a stratified random sample of the total adult population of Wadena, MN. The six-study strata were men and women from three age groups: young, 20-39 years of age; middle-aged, 40-59; and older, greater than 60 years of age. MEASUREMENTS: During a liquid meal of Ensure-Plus (Ensure-Plus challenge test; EPCT; Ross Laboratories), blood samples were taken for glucose, free fatty acids, creatinine, and C-peptide. Plasma C-peptide taken 90 minutes after the EPCT was used as a surrogate measure for insulin. Clinical tests included one-time samples for hemoglobin, glycosylated hemoglobin, plasma cholesterol, triglycerides, and lipoproteins. Physical measurements included height, weight, and blood pressure. Urine was assayed for C-peptide and creatinine. Assays of urine and plasma C-peptide used antibody M1221 (from Novo; Copenhagen, Denmark). MAIN RESULTS: No differences were observed for the relationship between age and C-peptide within each of the three age groups for men and the three age groups for women. However, the levels of plasma C-peptide for older men or women were statistically significantly higher than levels for the young age groups of the same sex; fasting plasma glucose also was higher for older groups of both sexes, and postmeal glucose was significantly higher for older women. There were decreases with age in urine C-peptide clearance for women and men; the decline for women was statistically significant. In multiple regression models for men alone and women alone, that controlled for age, post-meal plasma glucose best explained plasma C-peptide levels. For young men, plasma glucose alone provided the best prediction of plasma C-peptide levels; body mass index (BMI) and plasma glucose provided the best prediction for young women. For older men and both middle-aged and older women, a combination of urine C-peptide clearance and plasma glucose best predicted plasma C-peptide levels; for middle-aged men, BMI also contributed to the prediction. CONCLUSIONS: Secretion of insulin in response to an orally administered mixed meal is undiminished with age in non-diabetic adults.
Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome: the cardiovascular risk in Young Finns Study.
Since metabolic syndrome (MetS) is a collection of cardiovascular risk factors involving multiple signaling systems, we related the metabolic abnormalities associated with MetS with circulating microRNA profiles to pinpoint the affected signaling pathways. The blood microRNA profile, genome wide gene expression and serum NMR metabolomics were analyzed from 71 participants of the Young Finns Study. We found nine microRNAs that associated significantly with metabolites connected to MetS. MicroRNA-144-5p concentration correlated with glucose levels, hsa-1207-5p with glycosylated hemoglobin and hsa-miR-484 with metabolites related to insulin resistance. Hsa-miR-625-3p correlated with cholesterol levels, hsa-miR-1237-3p and hsa-miR-331-3p expression with certain fatty acids levels and hsa-miR-129-1-3p, -129-2-3p, and -1288-3p with glycerol levels. The down-regulated targets of miR-1207-5p and -129-2-3p were enriched in PI3K and MAPK pathways and 8 out of the 12 enriched pathways were down-regulated in individuals with MetS. In conclusion microRNAs associated with several aspects of MetS, possibly regulating glucose and lipid metabolism.
Abuse of alcohol may derange bone metabolism and cause osteoporosis. Due to confounding factors associated with alcohol abuse, however, the effect of alcohol itself on bone loss remains obscure. The influence of alcohol intake on bone and mineral metabolism is rather well known, but how the metabolism normalizes during withdrawal has rarely been investigated. The aims of the present study were to evaluate the alcohol-induced changes of bone and mineral metabolism and their recovery during abstention, and to reassess any possible link between alcohol abuse and osteoporosis.
We studied 27 non-cirrhotic male alcoholics hospitalized for 2 weeks for withdrawal. For comparison, three groups of control subjects were examined. Serum and urinary parameters of bone and mineral metabolism as well as intestinal absorption of calcium were determined at the beginning and end of the treatment period. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry at four axial sites (lumbar spine, femoral neck, Ward's triangle, trochanter).
On admission, bone formation in the alcoholics was reduced as reflected by decreased serum levels of osteocalcin (-28%; p
OBJECTIVES: Bedtime carbohydrate (CHO) intake in patients with type-2 diabetes may improve glucose tolerance at breakfast the next morning. We examined the 'overnight second-meal effect' of bedtime supplements containing 'rapid' or 'slow' CHOs. DESIGN: Randomized cross-over study with three test-periods, each consisting of two days on a standardized diet, followed by a breakfast tolerance test on the third morning. SETTING: The Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg, Sweden. SUBJECTS: Sixteen patients with type 2 diabetes on oral agents and/or diet. INTERVENTIONS: Two different bedtime (22.00 h) CHO supplements (0.46 g available CHO/kg body weight) were compared to a starch-free placebo ('normal' food regimen). The CHOs were provided as uncooked cornstarch (slow-release CHOs) or white bread (rapid CHOs). RESULTS: On the mornings after different bedtime meals we found similar fasting glucose, insulin, free fatty acid and lactate levels. However, the glycaemic response after breakfast was 21% less after uncooked cornstarch compared to placebo ingestion at bedtime (406 +/- 46 vs 511 +/- 61 mmol min l(-1), P
In a nested case-control study, calcium status was assessed by measurements of serum total calcium, magnesium, phosphate, ionized calcium, parathyroid hormone, albumin, total CO2 (bicarbonate), and free fatty acids in relation to gallstone formation. The subjects were recruited from a cohort study (n = 4,581) on the epidemiology of gallstones in Denmark. The cohort was examined with ultrasonography twice, in 1983 and 1988; 63 subjects developed gallstones, and among those who did not, 122 were randomly selected as controls. Subjects with gallstones had significantly increased serum concentrations of total calcium, magnesium, and bicarbonate as compared with normal subjects. The difference was only observed in women. Age, body mass index, alcohol consumption, and smoking did not influence the results when included as covariables in a logistic regression analysis. Multivariate analysis showed increased concentrations of magnesium, bicarbonate, and parathyroid hormone to be significantly associated with gallstone disease in women. No significant association was observed between gallstone disease and serum variables in men.