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Aims To test whether concomitant use of an automated bolus calculator for people with Type 1 diabetes carrying out advanced carbohydrate counting would induce further improvements in metabolic control. Methods We conducted a 12-month, randomized, parallel-group, open-label, single-centre, investigator-initiated clinical study. We enrolled advanced carbohydrate counting-naïve adults with Type 1 diabetes and HbA1c levels 64-100 mmol/mol (8.0-11.3%), who were receiving multiple daily insulin injection therapy. In a 1:1-ratio, participants were randomized to receive training in either advanced carbohydrate counting using mental calculations ( MC group) or advanced carbohydrate counting using an automated bolus calculator ( ABC group) during a 3.5-h group training course. For 12 months after training, participants attended a specialized diabetes centre quarterly. The primary outcome was change in HbA1c from baseline to 12 months. Results Between August 2012 and September 2013, 168 participants (96 men and 72 women) were recruited and randomly assigned to the MC group ( n = 84) and the ABC group ( n = 84). Drop-out rates were 23.8 and 21.4%, respectively ( P = 0.712); 130 participants completed the study. The baseline HbA1c was 75 ± 9 mmol/mol (9.0 ± 0.8%) in the MC group and 74 ± 8 mmol/mol (8.9 ± 0.7%) in the ABC group. At 12 months, change in HbA1c was significant within both groups: MC group: -2 mmol/mol (95% CI -4 to -1) or -0.2% (95% CI -0.4 to -0.1; P = 0.017) and ABC group: -5 mmol/mol (95% CI -6 to -3) or -0.5% (95% CI -0.6 to -0.3; P < 0.0001), but HbA1c reductions were significantly greater in the ABC group ( P = 0.033). No episodes of severe hypoglycaemia were reported. Conclusions People with Type 1 diabetes initiating advanced carbohydrate counting obtained significantly greater HbA1c reductions when guided by an automated bolus calculator ( NCT02084498). [ABSTRACT FROM AUTHOR]

Objective The positive metabolic outcome of Roux-en-Y gastric bypass ( RYGB) surgery may involve fibroblast growth factor 21 ( FGF21), in both the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal. Design Observational intervention trial. Patients and measurements Eight obese, nondiabetic patients underwent RYGB. Plasma FGF21 was measured both before and after surgery on three different days during oral glucose loads (25 g or 50 g glucose) or a mixed meal. Blood samples were taken right before the meal and at 15-min intervals until 90 min and at 150 min and 210 min relative to the start of the meal. Results Overall, fasting plasma FGF21 did not change significantly before and after surgery (262 ± 71 vs 411 ± 119 pg/ml), but for three subjects, fasting plasma FGF21 increased significantly after surgery. Furthermore, FGF21 levels increased significantly at t = 90 and t = 150 min in response to 50 g glucose, but not after a mixed meal. Conclusions In conclusion, the observed increase in postprandial plasma FGF21 in response to glucose and the lack of FGF21 response to a mixed meal may have important implications for the physiologic role of FGF21. The increase in postprandial FGF21 in response to glucose in the early postoperative period may contribute to the metabolic improvements observed after gastric bypass. [ABSTRACT FROM AUTHOR]

Aims Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. Methods Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. Results Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. Conclusion These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults. [ABSTRACT FROM AUTHOR]

Aims To investigate the prevalence of symptomatic obstructive sleep apnoea in unselected patients with Type 2 diabetes referred to a tertiary diabetes clinic. Methods In a cross-sectional design, all newly referred patients were offered a stepwise screening for obstructive sleep apnoea with: (1) The Berlin questionnaire; then, if indicative: (2) overnight home monitoring with the ApneaLink™ device. Patients with an apnoea-hypopnoea index ⩾ 5/h were offered referral for diagnostic polygraphy and treatment initiation. Results A total of 200 patients participated (61% men; age 59.6 ± 10.5 years, diabetes duration 8.3 ± 6.3 years and BMI 31.7 ± 6.7 kg/m2). According to the questionnaire, 106 patients showed 'high risk' of obstructive sleep apnoea, and 72 of these were referred to polygraphy based on ApneaLink screening corresponding to a prevalence of symptomatic obstructive sleep apnoea of 39%. Patients with symptomatic obstructive sleep apnoea had significantly higher BMI, poorer glycaemic control and lower plasma HDL cholesterol levels as compared with patients unlikely to have obstructive sleep apnoea. The groups were not different with respect to sex, age, diabetes duration, blood pressure, diabetic complications or medication use. In multiple regression analyses, age, BMI and HDL cholesterol levels were all significant, independent predictors of obstructive sleep apnoea. Conclusions At least one third of people with Type 2 diabetes referred to a diabetes clinic in Denmark has symptomatic obstructive sleep apnoea. Our data suggest higher age, a compromised plasma lipid profile and a more obese phenotype in patients with Type 2 diabetes who have obstructive sleep apnoea, highlighting the need to focus on screening and treatment of obstructive sleep apnoea in these patients. [ABSTRACT FROM AUTHOR]

Aims Diabetic foot disease and amputations severely reduce quality of life and have major economic consequences. The aim of this study was to estimate time trends in the incidence of lower-extremity amputations in Danish people with diabetes. Methods We studied major and minor lower-extremity amputations from 2000 to 2011 among 11 332 people with diabetes from the Steno Diabetes Center. Amputations were identified by linkage of the electronic medical system with the National Patient Registry. Sex-specific incidence rates of amputations by age, diabetes duration, calendar time and diabetes type were modelled by Poisson regression. Results From 2000 to 2011, 384 incident lower-extremity amputations (205 major, 179 minor) occurred during 100 495 years of patient follow-up. From 2000 to 2011, the incidence of all lower-extremity amputations decreased by 87.5% among men and 47.4% among women with Type 1 diabetes and by 83.3% among men and 79.1% among women with Type 2 diabetes ( P < 0.001). In particular, there was a decline in major lower-extremity amputations. In 2011, the incidence rates of major lower-extremity amputations were 0.25 (95% CI 0.07-0.82) among men and 0.21 (95% CI 0.06-0.71) among women per 1000 patient-years at age 50 years and 0.56 (95% CI 0.18-1.89) among men and 0.41 (95% CI 0.16-1.09) among women per 1000 patient-years at age 70 years. No significant change in incidence of minor amputations was observed. Conclusion The incidence of major lower-extremity amputations reduced significantly from 2000 to 2011 in Danish people with diabetes followed at a diabetes specialist centre. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to investigate associations between HbA1c recall by patients with Type 2 diabetes and self-management behaviours, patient activation, perception of care and diabetes distress. Methods In a cross-sectional survey, 993 patients with Type 2 diabetes reported their latest HbA1c. Validated scales measured self-management behaviours, patient activation, perception of care and diabetes distress. Self-reported HbA1c was compared with latest measured HbA1c. Using logistic regressions, associations between HbA1c recall and the variables of interest were investigated. Results Sixty-four per cent of patients recalled their latest HbA1c. Poor HbA1c recall was significantly associated with unhealthy eating behaviour, low level of exercise, low level of patient activation, poor glycaemic control, not knowing target HbA1c level, low educational level and being female. There were no associations between recall of HbA1c and diabetes distress or perceived care. Conclusions Recall of HbA1c level may increase patient activation and health-promoting behaviours. However, low educational level may be a barrier for using HbA1c as a motivator for health-promoting behaviours. This study indicates a need for studies of causal relationships, as well as mechanisms and challenges in using patient awareness of HbA1c as a driver for health-promoting behaviours. [ABSTRACT FROM AUTHOR]

Aims To develop risk scores for diabetes and diabetes or impaired glycaemia for individuals living in the Middle East and North Africa region. In addition, to derive national risk scores for Algeria, Saudi Arabia and the United Arab Emirates and to compare the performance of the regional risk scores with the national risk scores. Methods An opportunistic sample of 6588 individuals aged 30-75 years was screened. Screening consisted of a questionnaire and a clinical examination including measurement of HbA1c. Two regional risk scores and national risk scores for each of the three countries were derived separately by stepwise backwards multiple logistic regression with diabetes [HbA1c ≥ 48 mmol/mol (≥ 6.5%)] and diabetes or impaired glycaemia [HbA1c ≥ 42 mmol/mol (≥ 6.0%)] as outcome. The performance of the regional and national risk scores was compared in data from each country by receiver operating characteristic analysis. Results The eight risk scores all included age and BMI, while additional variables differed between the scores. The areas under the receiver operating characteristic curves were between 0.67 and 0.70, and for sensitivities approximately 75%; specificities varied between 50% and 57%. The regional and the national risk scores performed equally well in the three national samples. Conclusions Two regional risk scores for diabetes and diabetes or impaired glycaemia applicable to the Middle East and North Africa region were identified. The regional risk scores performed as well as the national risk scores derived in the same manner. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e382-e389 (2012) Abstract Aims To investigate the association between glycaemic control and patient socio-demographics, activation level, diabetes-related distress, assessment of care, knowledge of target HbA1c, and self-management behaviours, and to determine to what extent these factors explain the variance in HbA1c in a large Danish population of patients with Type 2 diabetes. Methods Cross-sectional survey and record review of 2045 patients from a specialist diabetes clinic. Validated scales measured patient activation, self-management behaviours, diabetes-related emotional distress, and perceived care. The electronic patient record provided information about HbA1c, medication, body mass index, and duration of diabetes. Data were analysed using multiple linear regression models with stepwise addition of covariates. Results The response rate was 54% ( n = 1081). Good glycaemic control was significantly associated with older age, higher education, higher patient activation, lower diabetes-related emotional distress, better diet and exercise behaviours, lower body mass index, shorter duration of disease and knowledge of HbA1c targets ( P < 0.05 for all). Patient socio-demographics, behaviour; perceptions of care and diabetes distress accounted for 14% of the total variance in HbA1c levels ( P = 0.0134), but the variance explained was higher for respondents treated with medications other than insulin. Conclusions Our study emphasizes the complex relationships between patient activation, distress and behaviour, specific treatment modalities and glycaemic control. Knowledge of treatment goals, achieving patient activation in coping with diabetes, and lowering disease-related emotional stress are important patient education goals. However, the large unexplained component of HbA1c variance highlights the need for more research to understand the mechanisms of glycaemic control. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e163-e169 (2012) Abstract Aim As both impaired fasting glucose and silent myocardial ischaemia are risk factors for cardiovascular disease and death, we hypothesized that these risk factors in combination would identify those subjects at the highest risk of adverse events. Methods Healthy individuals without diabetes ( n = 596, 55-75 years) were examined for silent myocardial infarction (≥ 1 mm ST-interval during ≥ 1 min) by ambulant 48-h continuous electrocardiogram monitoring and impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l). Results After 6.3 years, 77 subjects met the endpoint of myocardial infarction and/or death. The prevalence of silent myocardial ischaemia at inclusion was 12.3% in subjects with impaired fasting glucose and 11.7% in subjects with normal fasting glucose, P = 0.69. Subjects with impaired fasting glucose/silent myocardial ischaemia more often met the endpoint (36%) than subjects with impaired fasting glucose/no silent myocardial ischaemia (15%), subjects with normal fasting glucose/silent myocardial ischaemia (12%), and subjects with normal fasting glucose/no silent myocardial ischaemia (10%), respectively, ( P < 0.001). In a Cox model including these four study groups of interest, gender, age, smoking habits, blood pressure and total cholesterol, only subjects with impaired fasting glucose/silent myocardial ischaemia exhibited an increased risk of death or myocardial infarction (hazard ratio 2.5, P = 0.016). Conclusion The combination of impaired fasting glucose and silent myocardial ischaemia was associated with the poorest prognosis in middle-aged and older subjects without previously known glucose metabolic aberration and heart disease. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 654-661 (2012) Abstract Aims To investigate the relationship between structural and functional social support and patient activation, diabetes-related emotional distress, perceived diabetes care, self-management behaviour and HbA1c levels among patients with Type 2 diabetes. Methods Self-administered questionnaires were collected from 2572 patients with Type 2 diabetes. After adjusting for gender, age and education, Tobit and logistic regression models were used to examine associations between social network and patient activation, psychosocial problems, self-management behaviours and HbA1c levels. Results Frequent contact with friends was associated with more positive scores for activation, fewer psychosocial problems, more positive assessment of care and health-promoting self-management behaviours such as frequent exercising and frequent foot examinations. Frequent contact with family was associated with more positive assessments of care. Living with a partner was associated with lower prevalence of smoking, a higher frequency of foot examinations and higher HbA1c levels. A poor functional social network, measured as perceived lack of help in the event of severe illness, was associated with low patient activation, greater emotional distress, negative assessment of care, less health-promoting eating habits and less frequent foot examinations. Conclusions Good social support is significantly associated with health-promoting behaviours and well-being among patients with Type 2 diabetes. However, HbA1c levels are higher for cohabitant persons, indicating barriers for social support. Intervention research is needed to investigate the causal relationship between social networks and health-promoting behaviours. This knowledge should be used in clinical practice when targeting and designing education, support and care for patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: Skeletal muscle insulin resistance has been linked to mitochondrial dysfunction. We examined how improvements in muscular insulin sensitivity following rosiglitazone (ROSI) or pioglitazone (PIO) treatment would affect muscle mitochondrial function in patients with type 2 diabetes mellitus (T2DM). Methods: Muscle biopsies were obtained from 21 patients with T2DM before and after 12 weeks on either ROSI (4 mg once daily) [ n = 12; age, 59.2 ± 2.2 years; body mass index (BMI), 29.6 ± 0.7 kg/m2] or PIO (30 mg once daily) ( n = 9; age, 56.3 ± 2.4 years; BMI, 29.5 ± 1.5 kg/m2). An age- and BMI-matched control group was also included ( n = 8; age, 61.8 ± 2.3 years; BMI, 28.4 ± 0.6 kg/m2). Insulin sensitivity, citrate synthase- and β-hydroxyacyl-CoA-dehydrogenase (HAD) activity, intramuscular triglyceride (IMTG) and protein content of complexes I–IV were measured, while mitochondrial respiration per milligram muscle was measured in saponin-treated skinned muscle fibres using high-resolution respirometry. Results: Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls at baseline and decreased during ROSI treatment but increased during PIO treatment. Citrate synthase activity and average protein content of complexes I–IV were unchanged in the ROSI group, but protein content of complexes II and III increased during PIO treatment. Insulin sensitivity improved in all patients, but IMTG levels were unchanged. Conclusions: We show opposite effects of ROSI and PIO on mitochondrial respiration, and also show that insulin sensitivity can be improved independently of changes in mitochondrial respiration. We confirm that mitochondrial respiration is reduced in T2DM compared to age- and BMI-matched control subjects. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal. Objective: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients. Design: A randomized, stratified, multicentre trial having a 2 × 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months. Patient Population: Nine hundred and fifty patients with T2DM and HbA1c ≥ 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue. Randomization: Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre. Interventions: Metformin 1 g × two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with • Insulin detemir before bedtime (approximately 315 patients) or • Biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or • Insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c ≤ 7.0%. Outcome measures: Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome measures comprises the composite outcome of death, acute myocardial infarction, stroke or amputation assessed by an adjudication committee blinded to intervention, other cardiovascular clinical outcomes, average postprandial glucose increment from 0 to 18 months, hypoglycaemia and any inadvertent medical episodes. In addition, change in plaque formation in the carotids, HbA1c, cardiovascular biomarkers, body composition, progression of microvascular complications and quality of life will be assessed as tertiary outcome measures. Time schedule: Patient enrolment started May 2008. Follow-up is expected to finish in March 2011. Conclusion: CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aim: Several mechanisms have been targeted as culprits of weight gain during antihyperglycaemic treatment in type 2 diabetes (T2DM). These include reductions in glucosuria, increased food intake from fear of hypoglycaemia, the anabolic effect of insulin, decreased metabolic rate and increased efficiency in fuel usage. The purpose of the study was to test the hypothesis that mitochondrial efficiency increases as a result of insulin treatment in patients with type 2 diabetes. Methods: We included ten patients with T2DM (eight males) on oral antidiabetic treatment, median age: 51.5 years (range: 39–67) and body mass index (BMI): 30.1 ± 1.2 kg/m2 (mean ± s.e.). Muscle biopsies from m. vastus lateralis and m. deltoideus were obtained before and after seven weeks of intensive insulin treatment, and mitochondrial respiration was measured using high-resolution respirometry. State 3 respiration was measured with the substrates malate, pyruvate, glutamate, succinate and ADP. State 4o was measured with addition of oligomycine. An age, sex and BMI-matched control group was also included. Results: HbA1c improved significantly and the patients gained on average 3.4 ± 0.9 kg. Before treatment, respiratory control ratios (RCRs) of the T2DM were lower than the obese controls [2.6 vs. 3.2 (p < 0.05)], but RCR returned to the levels of the control subjects during treatment. Average state 4o of arm and leg declined by 14% (p < 0.05) during insulin treatment. Conclusions: Tight glycaemic control leads to reductions in inner mitochondrial membrane leak and increased efficiency of mitochondria. This change in mitochondrial physiology could contribute to the weight gain seen with antihyperglycaemic treatment. [ABSTRACT FROM AUTHOR]

AIMS: To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes. METHODS: Thirteen Type 1 patients were included, of whom 10 completed the cross-over study. Ten non-diabetic, matched control subjects were also examined. Body composition was estimated by dual-energy X-ray absorptiometry (DXA) whole-body scanning, diet intake was monitored by 7-day dietary record and insulin sensitivity was measured by the insulin clamp technique at baseline and after each of the diet intervention periods. RESULTS: On an isocaloric low-fat diet, Type 1 diabetic patients significantly reduced the proportion of fat in the total daily energy intake by 12.1% (or -3.6% of total energy) as compared with a conventional diabetes diet (P = 0.039). The daily protein and carbohydrate intake increased (+4.4% of total energy intake, P = 0.0049 and +2.5%, P = 0.34, respectively), while alcohol intake decreased (-3.2% of total energy intake, P = 0.02). There was a significant improvement in insulin sensitivity on the isocaloric, low-fat diet compared with the standard diabetes diet [7.06 +/- 2.16 mg/kg/min (mean +/- sd) vs. 5.52 +/- 2.35 mg/kg/min (P = 0.03)]. However, insulin sensitivity remained 33% lower than in the control subjects (P = 0.021). No significant changes occurred in body weight or body composition. Glycated haemoglobin rose during both diet intervention periods (P = 0.18), with no difference between the two diets. CONCLUSIONS: Change to an isocaloric, low-fat diet in Type 1 diabetic patients during a 3-month period resulted in significant improvement in insulin sensitivity without improvement in glycaemic control. However, insulin sensitivity remained 33% lower than in control subjects. [ABSTRACT FROM AUTHOR]

Aims To describe body composition in patients with Type 1 diabetes at diagnosis and during the first year after initiation of insulin therapy. Research design and methods In 10 (eight male and two female) newly onset Type 1 patients, age 31.5 ± 3.2 years (27-37 years) (SD and range), body mass index (BMI) 20.8 ± 1.6 (19.2-23.4) kg/m², body composition was estimated by means of dual-energy X-ray absorptiometry (DXA) whole body scanning supplemented by estimation of total body water (TBW) (isotope dilution technique with ³H[sub 2]O) at diagnosis and after 1, 3, 6 and 12 months of insulin therapy. Results During the first year after onset of diabetes body weight (BW) increased 4.3 ± 2.9 (0.1-8.3) kg (P = 0.0012) distributed as a 13.3% (1.6 kg) increase in total fat mass (FM) and 4.9% (2.5 kg) increase in lean body soft tissue mass (LBM). The self-reported weight loss at onset was 6.3 ± 2.5 kg (1.5-10.0 kg). Compared with two reference populations the Metropolitan Life Insurance Co. and a healthy age and sex-matched local DXA scanned group the initial body composition data demonstrated BW 6.2 kg below ideal weight and a significant reduction of the FM (25 % or -0.87 SD), whereas LBM was within the expected range. Conclusions During the first year after onset of Type 1 diabetes the mean increase in BW is 6.5% with a 13.3% increase in FM and a 4.9% increase in LBM. Selfreported data on premorbid BW suggest an approximately 10% reduction in BW at onset of Type 1 diabetes. Compared with a healthy reference population initial body composition data demonstrate a 25 % reduction of the FM, whereas only a minor and non-significant reduction in the LBM is encountered. These data indicate that uncontrolled diabetes is rather a fat catabolic state than, as previously believed, a protein catabolic state. [ABSTRACT FROM AUTHOR]

SUMMARY Aim To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI ), non-insulin mediated glucose disposal, glucose effectiveness (SG ) and β-cell function. Design Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet. Subjects Twelve obese patients (11 women, 1 man), age 45.8 ± 10.5 years, body weight (BW) 99.7 ± 13.3 kg, BMI 35.3 ± 2.8 kg/m2 . Measurements At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning. Results The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a 19% increase. A significant decrease in both fasting (p = 0.038) and 2 h (p = 0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI ) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = - 0.83, p = 0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in SI explaining 67% of the variation. First phase insulin response (AIRg) remained unchanged whereas insulin disposition index increased significantly (p = 0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later. Conclusion In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor... [ABSTRACT FROM AUTHOR]

We studied the effect of acute exposure, by constant intravenous infusion, to a low blood ethanol concentration (range 8-14 mmol/l) on the in vivo capacity of urea-N synthesis (CUNS), alanine elimination, and the nitrogen retention in fed and fasted rats. Alanine was infused to obtain a constant blood concentration of alpha-amino nitrogen between 7.3 and 11.7 mmol/l, at which concentrations urea synthesis is at maximum. CUNS was calculated after nephrectomy as accumulation of urea in body water, elimination of alanine as alanine infusion rate corrected for accumulation, and nitrogen retention as the difference. In the fed state ethanol decreased CUNS from 7.84 +/- 0.32 mumol N/(min 100 g body weight (BW] (mean +/- SEM) (n = 7) to 6.30 +/- 0.58 (n = 6) (p less than 0.001) and in the fasted state from 8.25 +/- 0.27 mumol N/(min 100 g BW) (n = 10) to 6.90 +/- 0.25 (n = 10) (p less than 0.001). In the fed state ethanol increased the elimination of alanine from 6.49 +/- 0.28 mumol/(min 100 g BW) (n = 7) to 6.95 +/- 0.25 (n = 6) (p less than 0.01), and in the fasted state decreased it from 6.25 +/- 0.12 mumol/(min 100 g BW) (n = 10) to 5.67 +/- 0.20 (n = 10) (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)