Self-rated work ability as a risk factor for disability retirement.

BACKGROUND: Simple and efficient survey measures to predict staying in or leaving work are needed. We examined the association of single-item self-rated work ability (SRWA) with disability retirement in two large population-based samples and compared the association of SRWA to two other scales, work ability score (WAS) and self-rated health (SRH), used earlier in studies. METHODS: The study population comprised 6034 participants aged 35-58 from the population-based Health 2000 and FinHealth 2017 cohort studies, pooled together. SRWA, WAS and SRH were all classified in three categories: poor, limited and good. A 36-month follow-up for disability retirement via linkage to electronic records was included in the analysis. RESULTS: Of the participants, 195 retired during the follow-up. All three measures strongly predicted disability retirement. Hazard ratio (HR) for poor SRWA (vs. good) was 8.48 [95% confidence interval (CI) 5.41-13.28], WAS 7.99 (95% CI 5.62-11.37) and SRH 5.96 (95% CI 4.17-8.51). HR for limited SRWA (vs. good) was 4.35 (95% CI 3.21-5.91), WAS 3.54 (95% CI 2.49-5.04) and SRH 2.27 (95% CI 1.59-3.23). Taking into account gender, age, education and mental health narrowed the gap between poor and limited vs. good work ability as predictors of disability retirement, but the differences remained clear. CONCLUSIONS: Limited or poor self-rated work ability or health are strong predictors of disability retirement. The SRWA measure is a useful survey-measure of work ability in community-based surveys.

Changes in healthy and unhealthy working life expectancies among older working-age people in Finland, 2000-2017.

BACKGROUND: Raising the statutory retirement age has been a common policy response to population ageing, but health problems may restrict labour force participation in older ages. We examined the development of healthy and unhealthy working life expectancies in Finland from 2000 to 2017 using different measures of health problems. METHODS: Healthy and unhealthy working life expectancies were calculated for the age range 50-65 years using the Sullivan method. The health measures were limiting long-standing illness, self-rated health, mental health problems and self-assessed work ability. RESULTS: Healthy working life expectancy was highest when health was measured by work ability. From 2000 to 2017, working years in full ability between the ages 50-65 increased from 6.2 (95% confidence interval 5.9-6.4) to 8.2 (8.0-8.5). Healthy working life expectancy increased also when measured by the other indicators. Unhealthy working years also increased, except when health problems were measured by limiting long-standing illness. The share of years in work increased both within the healthy and the unhealthy years, the increase being larger or equally large for the latter. Within the healthy and unhealthy years measured by the other three indicators, the share of working years increased irrespective of whether work ability was full or limited, but the increase was larger for limited work ability. CONCLUSIONS: In Finland, healthy working life expectancy has increased irrespective of how health is measured but also working with health problems has become more prevalent. The estimates for healthy working years are highest when a direct measure of work ability is used.

Life-course risk factor levels and coronary artery calcification. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Risk factors measured in early life have been shown to predict coronary artery calcium (CAC) in adulthood. However, limited data exist on when risk factor profiles of those who develop CAC diverge from those who do not. We investigated the associations of coronary heart disease risk factor trajectories beginning in adolescence and CAC measured at middle-age. METHODS: CAC was measured among 589 participants aged 39-45years in whom cardiovascular risk factors (serum lipids, blood pressure, body mass index, physical activity, smoking habits, and fruit, vegetable, fish, and butter intake) had been collected in 1980, 1983, 1986, 2001, and 2007 as part of the Cardiovascular Risk in Young Finns Study. RESULTS: Mean levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol, apolipoprotein B (Apo-B), and systolic blood pressure (SBP) levels across the 27-year period were significantly higher among those with CAC vs. those without. The difference between the groups was 0.25mmol/l (95% confidence interval, 95%CI, 0.079-0.41) for LDL-C, 0.26mmol/l (95%CI 0.080-0.44) for total cholesterol, 0.05mmol/l (95%CI 0.0085-0.091) for Apo-B and 1.92mmHg (95%CI 0.10-3.74) for SBP after adjustment for other risk factors. Those with CAC at age 39-45years had higher serum lipid levels already in adolescence or early adulthood compared with those without CAC, with these differences becoming more pronounced during the life-course. CONCLUSIONS: Long-time risk factor exposure to higher LDL-C, total cholesterol and Apo-B levels already starting in adolescence and higher SBP levels in adulthood is associated with CAC at middle-age.

Comprehensive MR Urography Protocol: Equally Good Diagnostic Performance and Enhanced Visibility of the Upper Urinary Tract Compared to Triple-Phase CT Urography.

OBJECTIVES: To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT) using a comprehensive 3.0T- magnetic resonance urography (MRU) protocol versus triple-phase computed tomography urography (CTU). METHODS: During the study period (January-2014 through December-2015), all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test. RESULTS: Twenty patients (39 UUT excreting units) were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU) and 87.2% (with CTU) and >75% visualization in 100% (3.0T-MRU) and 93.6% (CTU). Mean CTU effective radiation dose was 9.2 mSv. CONCLUSIONS: Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02606513.

Childhood Psychosocial Factors and Coronary Artery Calcification in Adulthood: The Cardiovascular Risk in Young Finns Study.

IMPORTANCE: There is increasing evidence supporting the importance of psychosocial factors in the pathophysiology of atherosclerotic disease. They have been shown to be associated with the population attributable risk for myocardial infarction. OBJECTIVE: To determine if a score of favorable childhood psychosocial factors would be associated with decreased coronary artery calcification in adulthood. DESIGN, SETTING, AND PARTICIPANTS: The analyses were performed in 2015 using data gathered in 1980 and 2008 within the longitudinal Cardiovascular Risk in Young Finns Study. The data source consisted of 311 individuals who had psychosocial factors measured at ages 12 years to 18 years and coronary artery calcification measured 28 years later in adulthood. The summary measure of psychosocial factors in childhood comprised measures of socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child. MAIN OUTCOMES AND MEASURES: Coronary artery calcification at ages 40 years to 46 years. RESULTS: Of the 311 participants, 48.2% were men. Of the participants, 55 (17.7%) had some calcium observed in their coronary arteries. A 1-SD increase in a favorable summary score of childhood psychological factors was associated with an adulthood coronary artery calcification probability of 0.85 (95% CI, 0.76-0.95) (P = .006). This inverse relationship remained significant after adjustment for age, sex, and conventional childhood risk factors (0.85; 95% CI, 0.74-0.97; P = .02) or for age, sex, adulthood conventional cardiovascular risk factors, socioeconomic status, social support, and depressive symptoms (0.83; 95% CI, 0.71-0.97; P = .02). CONCLUSIONS AND RELEVANCE: In this longitudinal study, we observed an independent association between childhood psychosocial well-being and reduced coronary artery calcification in adulthood. A positive childhood psychosocial environment may decrease cardiovascular risk in adulthood and may represent a potentially modifiable risk determinant.

Coronary heart disease risk factors, coronary artery calcification and epicardial fat volume in the Young Finns Study.

AIMS: We investigated associations of pre-clinical coronary heart disease (CHD), adolescence and adulthood CHD risk factors, and epicardial fat volume (EFV), which is thought to influence CHD pathology. METHODS AND RESULTS: EFV and coronary calcium scores were quantified using computed tomography imaging for 557 subjects from the Cardiovascular Risk in Young Finns Study in 2007. CHD risk marker levels were assessed repeatedly from 1980 to 2007. Carotid intima-media thickness (cIMT), carotid distensibility, and brachial flow-mediated dilatation were measured by vascular ultrasound in 2007. Increased EFV was cross-sectionally associated with male sex, increased waist circumference, body-mass index (BMI), cIMT, metabolic syndrome prevalence, levels of apolipoprotein B, total cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, blood pressure, insulin, and fasting glucose, as well as ever smoking, alcoholic intake, and lower high-density lipoprotein cholesterol (HDL-C), carotid distensibility and physical activity in adulthood. In BMI-adjusted analyses, only apolipoprotein B, ever smoking, alcohol intake and metabolic syndrome prevalence were independently associated with EFV. In adolescence, skinfold thickness, BMI, and insulin levels were higher and HDL-C lower with increasing EFV. Subjects in the lowest vs. highest quarter of EFV had consistently lower BMI across the early life-course. CONCLUSION: Associations of CHD risk markers with EFV were attenuated after multivariable adjustment. We found no evidence of increased EFV being independently associated with pre-clinical atherosclerosis. EFV was most strongly associated with BMI and waist circumference. Subjects with higher EFV had consistently higher BMI from age 12 suggesting that life-long exposure to higher BMI influences the development of EFV.

Imaging and Treatment Features of Idiopathic Pancreatitis and Pancreas Divisum in a Young Man: A Case Report.

Some patients with pancreas divisum (PD) develop symptoms of recurrent pancreatitis. This is probably caused by insufficient drainage of the pancreatic duct. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive test reported to be highly accurate in diagnosing PD. Endoscopic minor papilla sphincterotomy is most effective in the treatment of patients with PD and pancreatic stones. We report a case of 17-year-old boy who has suffered from several abdominal pain attacks throughout his childhood without a specific diagnosis. Radiological findings after the first episode of pancreatitis were typical for PD and led to specific treatment and cure.

Adolescence risk factors are predictive of coronary artery calcification at middle age: the cardiovascular risk in young Finns study.

OBJECTIVES: The purpose of this study was to examine the roles of adolescence risk factors in predicting coronary artery calcium (CAC). BACKGROUND: Elevated coronary heart disease risk factor levels in adolescence may predict subsequent CAC independently of change in risk factor levels from adolescence to adulthood. METHODS: CAC was assessed in 589 subjects 40 to 46 years of age from the Cardiovascular Risk in Young Finns Study. Risk factor levels were measured in 1980 (12 to 18 years) and in 2007. RESULTS: The prevalence of any CAC was 19.2% (27.9% in men and 12.2% in women). Age, levels of systolic blood pressure (BP), total cholesterol, and low-density lipoprotein cholesterol (LDL-C) in adolescence, as well as systolic BP, total cholesterol, diastolic BP, and pack-years of smoking in adulthood were higher among subjects with CAC than those without CAC. Adolescence LDL-C and systolic BP levels predicted CAC in adulthood independently of 27-year changes in these risk factors. The multivariable odds ratios were 1.34 (95% confidence interval: 1.05 to 1.70; p=0.02) and 1.38 (95% confidence interval: 1.08 to 1.77; p=0.01), for 1-SD increase in adolescence LDL-C and systolic BP, respectively. Exposure to both of these risk factors in adolescence (defined as values at or above the age- and sex-specific 75th percentile) substantially increased the risk of CAC (multivariable odds ratio: 3.5 [95% confidence interval: 1.7 to 7.2; p=0.007]) between groups with no versus both risk factors. CONCLUSIONS: Elevated adolescence LDL-C and systolic BP levels are independent predictors of adulthood CAC, indicating that adolescence risk factor levels play an important role in the pathogenesis of coronary heart disease.

Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans.

BACKGROUND & AIMS: Mechanisms leading to non-alcoholic steatohepatitis (NASH) have remained unclear, and non-invasive diagnosis of NASH is challenging. In this study, we investigated the benefits of measuring serum interleukin 1 receptor antagonist (IL-1RA) levels. METHODS: Liver biopsies from 119 morbidly obese individuals (47.5 ± 9.0 years, BMI 44.9 ± 5.9 kg/m(2)) were used for histological and gene expression assessment. In a cross-sectional population-based cohort of 6447 men (58 ± 7 years, BMI 27.0 ± 3.9 kg/m(2)) the association of serum IL1-RA with serum alanine aminotransferase (ALT) levels was investigated. RESULTS: Serum levels of IL-1RA, and liver mRNA expression of IL1RN are associated with NASH and the degree of lobular inflammation in liver (p<0.05). The decrease in serum IL-1RA level and expression of IL1RN after obesity surgery correlated with the improvement of lobular inflammation (p<0.05). We developed a novel NAFLD Liver Inflammation Score, including serum Il-1RA concentration, which performed better to diagnose NASH than did previously published scores. Results from the population study confirmed the potential of measuring serum IL-1RA level. The strongest determinants of the ALT concentration at the population level were Matsuda insulin sensitivity index (r(2)=0.130, p=7 × 10(-197)) and serum IL-1RA concentration (r(2)=0.074, p=1 × 10(-110)). IL-1RA concentrations associated significantly with ALT levels even after adjusting for BMI, alcohol consumption and insulin sensitivity (p=2 × 10(-21)). CONCLUSIONS: IL-1RA serum levels associate with liver inflammation and serum ALT independently of obesity, alcohol consumption and insulin resistance, suggesting a potential use of IL-1RA as a non-invasive inflammatory marker for NASH.

Dynamic MRI confirms support of the mid-urethra by TVT and TVT-O surgery for stress incontinence.

OBJECTIVE: To study changes in mid-urethral function with dynamic MRI in stress urinary incontinent women undergoing either tension-free vaginal tape (TVT) or TVT-obturator sling operations. DESIGN: Prospective clinical study. SETTING: University hospital. SAMPLE: Forty-two parous women with stress urinary incontinence recruited to dynamic magnetic resonance imaging before and after mid-urethral sling surgery. Control group of 16 healthy women. METHODS: Dynamic magnetic resonance imaging at rest, during pelvic floor muscle contraction, coughing and voiding with a bladder volume of 200-300 ml. X- and Y- coordinates were used to determine the location of the mid-urethra during these activities. MAIN OUTCOME MEASURES: Changes in mid-urethral position after TVT and TVT-obturator operations during the different activities. RESULTS: Postoperatively the women could elevate their mid-urethra by pelvic floor muscle contraction significantly higher than before the operation (p<0.05). Despite a different support angle between the TVT and the TVT-O mid-urethral slings, we could not see any differences in the movement patterns. CONCLUSION: Mid-urethral slings support the mid-urethra and restrict downward movement during different activities. Movement patterns are similar after TVT and TVT-O operations.

Dynamic magnetic resonance imaging of the behavior of the mid-urethra in healthy and stress incontinent women.

OBJECTIVES: Support of the mid-urethra is thought to be an essential element of urinary continence in the female. Our aim was to image the behavior of the mid-urethra in healthy volunteers and in stress urinary incontinence (SUI) patients by dynamic magnetic resonance imaging (MRI). DESIGN: Prospective study. SETTING: Gynecology outpatient clinic association with Department of Radiology in University Hospital of Kuopio, Finland. SAMPLE AND METHODS: Fifteen healthy volunteers and 40 SUI women underwent dynamic MRI at rest, during pelvic floor muscle contraction, coughing and voiding with a bladder volume of 200 ml. Our aim was to determine the precise location and movement of the mid-urethra during these activities. MAIN OUTCOME MEASURE: The co-ordinate location and movement of the mid-urethra. RESULTS: Continent volunteers can elevate their mid-urethra significantly higher than incontinent women. Moreover, the mid-urethra of incontinent women rotated significantly more dorsocaudally during straining and coughing than in continent women. CONCLUSIONS: Elevation of the mid-urethra was more marked in continent compared to urinary incontinent women on pelvic floor muscle contraction suggesting sufficient support of the urethra. Downward movement of the mid-urethra was more significant in stress incontinent women than in continent volunteers.

SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity.

OBJECTIVE: Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents. No studies are available in humans to demonstrate that SIRT1 expression in insulin-sensitive tissues is associated with energy expenditure and insulin sensitivity. RESEARCH DESIGN AND METHODS: Energy expenditure (EE), insulin sensitivity, and SIRT1 mRNA adipose tissue expression (n = 81) were measured by indirect calorimetry, hyperinsulinemic-euglycemic clamp, and quantitative RT-PCR in 247 nondiabetic offspring of type 2 diabetic patients. RESULTS: High EE during the clamp (r = 0.375, P = 2.8 x 10(-9)) and high DeltaEE (EE during the clamp - EE in the fasting state) (r = 0.602, P = 2.5 x 10(-24)) were associated with high insulin sensitivity. Adipose tissue SIRT1 mRNA expression was significantly associated with EE (r = 0.289, P = 0.010) and with insulin sensitivity (r = 0.334, P = 0.002) during hyperinsulinemic-euglycemic clamp. Furthermore, SIRT1 mRNA expression correlated significantly with the expression of several genes regulating mitochondrial function and energy metabolism (e.g., peroxisome proliferator-activated receptor gamma coactivator-1beta, estrogen-related receptor alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A), and with several genes of the respiratory chain (e.g., including NADH dehydrogenase [ubiquinone] 1alpha subcomplex 2, cytochrome c, cytochrome c oxidase subunit IV, and ATP synthase). CONCLUSIONS: Impaired stimulation of EE by insulin and low SIRT1 expression in insulin-sensitive tissues is likely to reflect impaired regulation of mitochondrial function associated with insulin resistance in humans.

Cholesterol absorption decreases after Roux-en-Y gastric bypass but not after gastric banding.

The differences in cholesterol metabolism after the 2 most common forms of obesity surgery, Roux-en-Y gastric bypass (RYGB) and gastric banding (GB), have not been well characterized. In this study, effects of RYGB and GB on cholesterol absorption and synthesis were investigated. To this aim, 1-year follow-up of cholesterol metabolism in 2 nonrandomized cohorts undergoing either RYGB (n = 29; age, 45.2 +/- 7.7 years; body mass index [BMI], 46.0 +/- 6.1 kg/m(2)) or GB (n = 26; age, 45.9 +/- 8.6 years; BMI, 50.1 +/- 7.7 kg/m(2)) was performed in a university hospital center specializing in the treatment of morbid obesity. Serum markers of cholesterol synthesis (cholestenol, desmosterol, and lathosterol) and cholesterol absorption (campesterol, sitosterol, avenasterol, and cholestanol) were measured preoperatively and at follow-up and expressed as ratios to cholesterol. As expected based on observed weight loss (25% after RYGB and 17% after GB, P < .001 between groups), both operations decreased serum levels of cholesterol synthesis markers by 12% to 28% (all Ps < .001). A decrease in cholesterol absorption markers was only observed after RYGB (-26% for sitosterol) and not after GB (+16%, P = 2 x 10(-6) for difference between the groups). The difference in sitosterol ratio between the groups remained significant after adjustment for age, BMI, fasting insulin levels, and nutritional status (P = 2 x 10(-4)), indicating a specific effect related to RYGB. We conclude that decrease in cholesterol absorption is a novel beneficial effect of RYGB. Together with an improved control of blood glucose, this may contribute to a better cardiovascular risk profile after RYGB.

Division of the hepatic branch of the anterior vagus nerve in fundoplication: effects on gallbladder function.

BACKGROUND: Cutting the hepatic branch of the anterior vagus nerve makes laparoscopic fundoplication technically easier; however, there is little data about the effect of cutting the nerve on gallbladder function. METHODS: One surgeon (MPä) preserved this nerve until March 2001 when he changed the technique. We investigated patients consecutively operated on before and after this date. A symptom questionnaire was returned by 59 patients, of whom 19 in both groups were successfully further investigated. The follow-up varied from 4 to 9 years postoperatively. The volume of the gallbladder was measured by ultrasonography before and after a fatty test meal. Alkaline phosphatase (ALP), alanine aminotransferase (ALAT), bilirubin, and amylase were determined from plasma. RESULTS: There was no difference in symptoms or use of antireflux medication between the groups. No difference was found in the levels of bilirubin, ALAT, or ALP. A mild elevation in plasma amylase was noted after nerve division (p = 0.041). The gallbladder ejection fraction did not differ between groups, but the fasting gallbladder volume was smaller when the nerve was cut (median 18.1 (range, 6-57.7) ml versus median 23.2 (range, 7.9-66.7) ml; p = 0.049). Both differences in plasma amylase and gallbladder fasting volume were clearer in male patients. CONCLUSIONS: Cutting the hepatic branch of the anterior vagus nerve during fundoplication may reduce the size of gallbladder, but it has no effect on the ejection fraction. No clinical significance has been noted to date. Prospective trials will be necessary to confirm these findings.

Placenta percreta: methotrexate treatment and MRI findings.

Our patient was a 24-year-old gravida 2 para 0 woman. After delivery, placenta percreta was noticed. There was no postpartum hemorrhage, and the patient desired future pregnancies. Although placenta percreta is rare, its sequelae include potentially lethal hemorrhage and loss of reproduction function. Placenta percreta was confirmed histologically and with ultrasonography and magnetic resonance imaging (MRI). Placenta percreta was treated conservatively with methotrexate. On follow-up, MRI showed a small calcified transmural extension of the placenta throughout the uterus in the right fundal area. Color Doppler ultrasonography showed no blood flow in the corresponding area, and maternal serum human chorionic gonadotropin (hCG) was undetectable. Use of MRI is a new method to detect abnormal placentation, and it could be used on follow-up in selective cases with other follow-up modalities. However, it seems likely that conservative management to preserve future fertility remains a secured and reasonable alternative when a patient has no active bleeding.

Markers of endothelial dysfunction and low-grade inflammation are associated in the offspring of type 2 diabetic subjects.

The offspring of type 2 diabetic patients are at elevated risk for type 2 diabetes and cardiovascular disease. The aim of our study was to characterize the role of various biomarkers of endothelial activation in a cohort of offspring of type 2 diabetic subjects and to assess the association of adhesion molecules with inflammatory markers and metabolic parameters. Cytokine and adhesion molecule levels were measured in 19 healthy subjects and in 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance and 20 with impaired glucose tolerance). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography. The levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-Selectin and vascular adhesion protein-1 were not increased in offspring of type 2 diabetic subjects, but they correlated with inflammatory markers (C-reactive protein, tumor necrosis-alpha, interleukin-6, interleukin-1 beta, interleukin-1 receptor antagonist, interleukin-8, interleukin-10 and interleukin-18). In conclusion, the levels of adhesion molecules were not elevated in the prediabetic state. Inflammatory markers and adhesion molecules were correlated suggesting that low-grade inflammation may precede the elevation of levels of adhesion molecules.

Single nucleotide polymorphisms of the melanocortin-3 receptor gene are associated with substrate oxidation and first-phase insulin secretion in offspring of type 2 diabetic subjects.

CONTEXT: The melanocortin-3 receptor (MC3R) is a part of the melanocortin system that regulates appetite and energy metabolism. The Thr/Thr 6 and Val/Val81 [corrected] polymorphisms of the MC3R gene have been previously associated with high insulin levels and obesity in children. OBJECTIVE: The objective was to determine whether single nucleotide polymorphisms (SNPs) of MC3R are associated with glucose, lipid, and energy metabolism. DESIGN, SETTING, AND PARTICIPANTS: We screened the Lys/Thr6 and Ile/Val81 mutations and six noncoding SNPs of MC3R in a cross-sectional study of 216 middle-aged nondiabetic Finnish subjects who were offspring of type 2 diabetic patients. MAIN OUTCOME MEASURES: Insulin secretion was evaluated by an iv glucose tolerance test, and insulin sensitivity and energy metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry. RESULTS: Carriers of the Lys 6 and Ile 81 [corrected] alleles had significantly lower rates of lipid oxidation [0.85 +/- 0.38 vs. 1.00 +/- 0.43 mg/kg of lean body mass (LBM)/min; P = 0.022, adjusted for sex, body mass index, age, and family relationship] and higher rates of glucose oxidation in the fasting state (11.28 +/- 4.64 vs. 9.71 +/- 4.53 micromol/kg of LBM/min; P = 0.031) than subjects with the Thr/Thr 6 and Val/Val 81 [corrected] genotypes. They had lower rates of lipid oxidation during the hyperinsulinemic clamp (0.32 +/- 0.41 vs. 0.44 +/- 0.34 mg/kg of LBM/min; P = 0.021) and higher insulin levels in an iv glucose tolerance test (insulin under the curve during the first 10 min, 3220 +/- 1765 vs. 2454 +/- 1538 pmol/liter.min; P = 0.025) compared to subjects with the common genotypes. CONCLUSIONS: Our results suggest that SNPs of MC3R may regulate substrate oxidation and first-phase insulin secretion.

Single nucleotide polymorphisms of the MCHR1 gene do not affect metabolism in humans.

Melanin concentrating hormone receptor-1 (MCHR1) is a centrally and peripherally expressed receptor that regulates energy expenditure and appetite. Single nucleotide polymorphisms (SNPs) of the MCHR1 gene have been previously associated with obesity, but the results are inconsistent among different populations. This study was performed to determine whether SNPs of MCHR1 affect glucose and energy metabolism. We screened six SNPs of MCHR1 in a cross-sectional study of 217 middle-age, non-diabetic Finnish subjects who were offspring of type 2 diabetic patients. Insulin secretion was evaluated by an intravenous glucose tolerance test and insulin sensitivity and energy metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry. SNPs of MCHR1 were not associated with BMI, waist circumference, subcutaneous or intra-abdominal fat area, glucose tolerance, first-phase insulin release, insulin sensitivity, or energy metabolism. One SNP, which was in >0.50 linkage disequilibrium with the other five SNPs, was also screened in 1455 unrelated Finnish middle-age subjects in a population-based study. No differences in BMI, waist circumference, or glucose or insulin levels in an oral glucose tolerance test among the genotypes were found. In conclusion, SNPs of MCHR1 did not have effects on metabolic variables in humans.

Changes in inflammatory cytokines are related to impaired glucose tolerance in offspring of type 2 diabetic subjects.

OBJECTIVE: We sought to determine whether levels of inflammatory markers and different cytokines are abnormal in nondiabetic offspring of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Cytokine levels were measured in 19 healthy control subjects and 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance [NGT] and 20 with impaired glucose tolerance [IGT]). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography. RESULTS: Levels of C-reactive protein and inflammatory cytokines were elevated in nondiabetic offspring of type 2 diabetic subjects. Interleukin (IL)-1beta was increased in the NGT group and decreased in the IGT group. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) were increased in both groups. IL-1beta and -Ra levels correlated inversely (P < 0.05) with rates of whole-body glucose uptake and IL-1beta positively with visceral fat mass (P < 0.05) in normoglycemic offspring. CONCLUSIONS: Nondiabetic offspring of type 2 diabetic subjects have changes in the levels of inflammatory cytokines. The level of IL-1Ra seems to be the most sensitive marker of cytokine response in the pre-diabetic state.