Jens Peter Kroustrup

In the Western world the number of obese people is increasing, but in Denmark the incidence is not on the same scale as in the USA. Although several factors may be of importance, Danes are more physically active and their intake of beverages with added sugar is less than in the American population.

Results from a phase II trial with Tesofensine for treatment of obesity are presented. In total 203 obese persons were randomised to treatment with Tesofensine 0.25, 0.5, or 1.0 mg, or placebo daily for 24 weeks. Treatment with Tesofensine resulted in a mean weight reduction of 4.5, 9.2 and 10.6% higher than that of placebo for 0.25, 0.5 and 1.0 mg, respectively. Tesofensine 0.5 mg might have the potential to produce a weight loss twice that of currently approved anti-obesity drugs. Findings of safety and efficacy of 0.5 mg Tesofensine need confirmation in phase III trials.

... 30 år bagud i forhold til amerikanske forhold [8]. Dette synes også at være tilfældet for yngre mænd til session, hvor 7% var fede i 2003 [9], hvilket er langt mindre end for rekrutter i det amerikanske flyvevåben [10]. ... 13. Berentzen T, Dalgaard LT, Petersen L, et al. ...

The Lancet Editors (April 6, p 1167) recently expressed concern regarding issues raised by the Danish Health and Medicines Authority (DHMA) audit of two of the fi ve clinical sites and the sponsor of our study reported in The Lancet. We appreciate this opportunity to clarify the issues. The audit found that investigators were wrongly instructed by the monitors not to register headache, migraine, stress, and depression as adverse events if patients reported these conditions before randomisation, leading to possible under-reporting of these adverse events. The audit found no diff erence in data reporting between the two inspected and three uninspected sites, suggesting that there was no diff erence in reporting of adverse events between sites. Our subsequent comparison of adverse events at the inspected sites with the other centres fi nds 55 (12%) versus 70 (11%) incidences of these specifi c adverse events, and 414 (88%) versus 556 (89%) of all adverse events (p=0·779, χ2 test). An analysis of other apparent. As stated by William Kannel, hypertension clusters with dyslipidaemia, insulin resistance, glucose intolerance, and obesity; and about 50% of patients with essential hypertension are insulin resistant, glucose intolerant, and dyslipidaemic as compared with equally hypertensive individuals who are insulin sensitive. More importantly, the development of cardiovascular disease is enhanced in the insulinresistant subgroup of patients with hypertension. For example, Jeppesen and colleagues reported that patients with essential hypertension whose triglycerides and HDL-cholesterol concentrations were in the lower third and upper third, respectively, were not at increased risk of cardiovascular disease, whereas the greatest incidence of cardiovascular disease was recorded in the hypertensive patients with the highest triglycerides and lowest HDL-cholesterol concentrations. Further more, the study by Sheu and colleagues of patients with hypertension without clinical evidence of cardiovascular disease showed that only the insulinresistant subgroup had evidence of cardiovascular disease. Additionally, the insulin-resistant subgroup was glucose intolerant, hyper insulinaemic, and dyslipidaemic when compared with insulin-sensitive patients with a similar degree of hypertension. No one can argue with an appeal to modify lifestyle behaviour to help to prevent the development of hypertension, nor the goal of lowering blood pressure if pharmacological intervention is required. However, one can argue that this approach is not suffi cient in at least 50% of patients with hypertension who are insulin resistant and have a metabolic profi le known to increase risk of cardiovascular disease. Eff orts to decrease long-term complications of high blood pressure will be limited to the degree that these other risk factors are not sought for or addressed.

A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States. This retrospective cohort study included 191 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. In multivariate analysis, hazard ratios for overall survival under the current AJCC TNM staging system vs the proposed TNM groupings with stage I as reference were 1.32 (95% CI: 0.38–4.57) vs 3.04 (95% CI: 1.38–6.67) for stage II, 2.06 (95% C...

Recent studies have shown a significant increase in the temporal trend of medullary thyroid carcinoma (MTC) incidence. However, it remains unknown to which extent sporadic medullary thyroid carcinoma (SMTC) and hereditary MTC (HMTC) affect the MTC incidence over time. We conducted a nationwide retrospective study using previously described RET and MTC cohorts combined with review of medical records, pedigree comparison and relevant nationwide registries. The study included 474 MTC patients diagnosed in Denmark between 1960 and 2014. In the nationwide period from 1997 to 2014, we recorded a mean age-standardized incidence of all MTC, SMTC and HMTC of 0.19, 0.13 and 0.06 per 100,000 per year, respectively. The average annual percentage change in incidence for all MTC, SMTC and HMTC were 1.0 (P = 0.542), 2.8 (P = 0.125) and −3.1 (P = 0.324), respectively. The corresponding figures for point prevalence at January 1, 2015 were 3.8, 2.5 and 1.3 per 100,000, respectively. The average annua...

Multiple endocrine neoplasia (MEN) 2A and 2B are caused by REarranged during Transfection (RET) germline mutations. In a recent nationwide study we reported of an unusually high prevalence (33%) of families with the C611Y mutation and hypothesized that this might be due to a founder effect. We conducted the first nationwide study of haplotypes in MEN2A families aiming to investigate the relatedness and occurrence of de novo mutations among Danish families carrying similar mutations. The study included 21 apparently unrelated MEN2A families identified from a nationwide Danish RET cohort from 1994 to 2014. Twelve, two, two, three and two families carried the C611Y, C618F, C618Y, C620R and C634R mutation, respectively. Single nucleotide polymorphism chip data and identity by descent analysis were used to assess relatedness. A common founder mutation was found among all 12 C611Y families and between both C618Y families. No relatedness was identified in the remaining families. Our data s...

The prevalence of overweight and obesity is escalating globally, and in Denmark more than 10% of the population are now severely overweight. The aim of this study was to estimate the short-term health effects of 15 weeks of intensive lifestyle intervention composed of physical activity, dietary changes and personal development in severely obese subjects of both sexes. The 27 subjects were weighed weekly. Fat percentage, abdominal circumference, maximum oxygen uptake, heart rate, oral glucose tolerance and blood lipids were measured at baseline and in week 15. The intensive lifestyle intervention was completed under supervision at a stay at Ebeltoft Kurcenter, and the goal was a weight loss of approximately 1% per week. At baseline, the participants' average body mass index (BMI: kg/m2) was 44 +- 1; the BMI was reduced by 11% after the stay (p<0.001). Body weight was reduced by 14 +- 4 kg (p<0.001), corresponding to 76% of the desired weight loss. The subjects' fat mass...

An unbiased counting rule for the number of topologically simple objects of any shape, size and distribution in 3D space is a pertinent problem in stereology. Combining the disector principle with the object's 3D Euler number makes possible number estimation, which until now has been obtainable only by exhaustive serial sections. The disector is a set of two sections where the object's profiles in one section are compared with its profiles on the neighbouring section, and the number of new 2D topological events is recorded. In a disector of known volume the sum of topological events is a direct estimate of the disector contribution to the total Euler number, which forms the basis for an ultimate number estimator in 3D, the ConnEulor. The method is illustrated by an electron microscopic study of the number of mitochondria in the exocrine cells of the pancreas.

Abstract: Extent of intra-abdominal fat had significant linear relations with six metabolic coronary risk factors: systolic and diastolic blood pressure, fasting blood concentrations of glucose, high density lipoprotein (HDL) cholesterol, triglyceride, and plasminogen activator inhibitor-1. Tumor necrosis factor-α and adiponectin can be biological mediators from the intra-abdominal fat to the metabolic coronary risk factors. Complementarily, we describe a new study that will analyze the gene expression in intra-abdominal and subcutaneous fat on mRNA and protein level using high throughput methods. The study will elucidate further whether intra-abdominal obesity is the common denominator for the different components of the metabolic syndrome.

Background Morbid obesity defined as BMI > 40 is a growing problem. It is primarily treated with diet, lifestyle changes, and medicine. However, at present, surgery remains the only effective option for the management. Methods Seventeen patients were studied 2 months after laparoscopic gastric banding. The aims were to evaluate the association between (1) the extent of pouch filling and satiety, (2) gastric emptying and weight loss, and (3) the pouch pressure during a meal and the sensation of satiety and weight loss. Results The preoperative weight was 146 kg (range 108–202 kg). The average weight loss was 21 kg between the banding and the examination. The half time (T 50%) for the pouch emptying was 3 min (quartiles 3–12.5) and the time to 90% of pouch emptying (T 90%) was 40 min (24.5–60). The sensation of satiety lasted 75 min (57.5–105), and the feeling of hunger started after 90 min (40–90). Neither T 50% nor T 90% correlated to the weight loss (R = 0.006, P > 0.5 and R = 0.1, P > 0.5). The sensation of satiety did not correlate to T 50% or T 90% (R = 0.6, P = 0.12 and R = 0.5, P = 0.15). No association was found between the sensory data and the pressure decline. Significant association was found between the load of the meal expressed as the area under the pouch pressure curve and the weight loss (R = 0.786, P = 0.015). Conclusion The satiety sensation lasted much longer than the pouch emptying and the pressure increase. The pressure load correlated to the weight loss. This indicates that neuroendocrine mechanisms caused by the accumulated mechanical load are most important for maintaining satiety.

The extracellular domain of the insulin-like growth factor II/mannose-6-phosphate receptor (IGF-II/M6P-R) is present in the circulation, but its relationship with plasma IGF-II is largely unknown. As IGF-II appears to be nutritionally regulated, we studied the impact of obesity, type 2 diabetes (T2D) and weight loss on circulating levels of IGF-II and its soluble receptor. Twenty-three morbidly obese non-diabetic subjects were studied before and after gastric banding (GB), reducing their BMI from 59.3+/-1.8 to 52.7+/-1.6 kg/m(2). Lean controls (n=10, BMI 24.2+/-0.5 kg/m(2)), moderately obese controls (n=21, BMI 31.8+/-1.0 kg/m(2)) and obese T2D patients (n=20, BMI 32.3+/-0.8 kg/m(2)) were studied before and after a hyperinsulinaemic euglycaemic clamp. Morbidly obese subjects had elevated IGF-II/M6P-R and IGF-II levels, which both decreased following GB (IGF-II/M6P-R: from 0.97+/-0.038 to 0.87+/-0.030 nmol/l, P=0.001; IGF-II: from 134+/-7 to 125+/-6 nmol/l, P=0.01), as did fasting plasma glucose and insulin (P<0.05). However, the metabolic parameters correlated with neither IGF-II nor IGF-II/M6P-R. Obese diabetics had increased IGF-II/M6P-R as compared with lean and obese controls (0.82+/-0.031 vs. 0.70+/-0.033 vs. 0.74+/-0.026 nmol/l; P<0.03) and levels were unaffected by clamp. In the latter cohort, IGF-II/M6P-R but not IGF-II correlated with HbA1c, and fasting plasma C-peptide, insulin and glucose (0.34<r<0.45; P<0.05). In all subjects, BMI correlated with IGF-II/M6P-R (r=0.57; P<0.001) and IGF-II (r=0.39; P<0.005). IGF-II/M6P-R and IGF-II were not associated. Serum IGF-II/M6P-R is up-regulated in morbid obesity, down-regulated by weight loss and elevated in moderately obese T2D. However, although plasma IGF-II was also reduced following GB, the two peptides were not statistically correlated. No acute effect of insulin was seen. These findings indicate that the IGF-II/M6P-R is nutritionally regulated, independently of IGF-II.