Adaptation to climate change on arable farms in the Dutch province of Flevoland. An inventory for the AgriAdapt project

In Flevoland, arable farming is the most dominant land use. Adaptation options related to water, pests and diseases have been studied using a literature review. The green-blue zone Oostvaarderswold in Flevoland contributes to water storage, to nature conservation and to recreation. Compensation costs for structural wetting that are associated with various frequencies of flooding have been calculated. At inundation frequencies greater than once in 5 years, buying the agricultural land might be a better option than compensating for inundation damage or income loss. Various policies will have an effect on future agriculture in the province. A literature survey of spatial policy plans shows that urbanisation will increase and that some cities, like Almere, Lelystad, Dronten and Emmeloord, will continue to grow and expand. As a consequence, more inhabitants will require more space for nature and recreational activities, which in turn will lead to agricultural land being required

Comparison of the accuracy of resting energy expenditure assessment using bioimpedance analysis and indirect respiratory calorimetry in children with simple obesity

Background: Assessment of resting energy expenditure (REE) is necessary for the formation of a diet for obesity patients. The «gold standard» for assessment of resting energy expenditure (REE) is indirect respiratory calorimetry. Currently, bioimpedance analyzers are increasingly being used in clinical practice to assess energy consumption at rest, including in obese children. However, the accuracy of such an assessment remains unclear.Aims: To determine the accuracy of the assessment of resting energy expenditure using bioimpedance analysis in children with simple obesity compared with indirect respiratory calorimetry.Materials and methods: Resting energy expenditure was assessed by bioimpedance analysis, Harris-Benedict formula and indirect respiratory calorimetry in all obese children. Comparability of methods was assessed using the Bland-Altman analysis.Results: The study included 320 children aged 7 to 17 years with simple obesity.Resting energy expenditure assessed by bioimpedance analysis was on average 232 kcal lower than the actual. A significant CI (-448 to 912 kcal) was revealed, as well as a large LOA from -514 to 979 kcal. REE calculated by the Harris-Benedict formula on average corresponded to the actual one, and CI varied from -38 to 27 kcal. However, large LOA from -514 to 979 kcal, indicating a high individual variability of resting energy consumption.Conclusions: Bioimpedance analyzers underestimate REE in obese children compared to indirect respiratory calorimetry and the Harris-Benedict formula. Given the significant discrepancies in the accuracy of REE assessment, bioimpedance analysis cannot be considered as an alternative to indirect respiratory calorimetry to assess resting energy in children with simple obesity

Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients

BACKGROUND: Monogenic diabetes mellitus (MDM) is a rare form of diabetes mellitus (DM) which caused by one or more mutations in one of the genes that cause pancreatic β-cell dysfunction. Despite the sufficient knowledge of the most common subtypes of MODY, cases of MDM are undiagnosed and classified as type 1 diabetes mellitus and type 2 diabetes mellitus.AIM: To study the clinical, laboratory characteristics, as well as age-related features of GCK-MODY in children.MATERIALS AND METHODS: The studied population is patients with GCK-MODY under the age of 18 years. The diagnosis was confirmed by genetic test, a heterozygous mutation was identificated in the GCK gene.RESULTS: MODY-GCK was verified in 144 patients (131 probands and 13 siblings) under the age of 18 years. Missense mutations were detected in 80.2% (n=105). Mutation was detected in one case in 59.6%. The most common missense mutations were p.G261R (n=7) and p.G258C (n=6). The age of diagnosis of carbohydrate metabolism disorders was 7.6 years [4.0; 11.2]. In 72.2% carbohydrate metabolism disorders were diagnosed accidentally, in 16.7% the examination was provided due to a family history of diabetes, 11.1% had clinical symptoms of diabetes. Fasting glycemia at diagnosis was 6.8 mmol / l [6.4; 7.3], HbA1c — 6.4% [6.1; 6.7]. At examination, the level of fasting glycemia corresponded to normal values in 16.4% of patients, impaired fasting glycemia — in 57.8%, diabetic — in 25.8%. In 62.3% of patients was impaired glucose tolerance, in 18.9% — to diabetic values, and in 11.7% of patients — to a normal level at 120 minutes during the oral glucose tolerance test. A moderate positive correlation was found between the age of examination and the levels of fasting glycemia (r=0.347, p<0.01), C-peptide (r=0.656, p<0.001), and insulin (r=0.531, p<0.001). Insulin resistance (IR) (HOMA index) was detected in 21 patients (14.5%), obesity — in 6 patients (4.2%). In 9 patients (6.25%) was revealed a moderate increase in the titer of specific pancreatic antibodies (AT). The presence of IR, obesity, AT did not affect the level of HbA1c. In 92.3% diet was priscribed, in 4.2% insulin was prescribed, 2.1% — metformin, 1.4% — sulfonylureas.CONCLUSION: In children, disorders of carbohydrate metabolism in GCK-MODY are diagnosed accidentally, asymptomatically at any age from birth, and are characterized by a combination of impaired fasting glycemia and impaired glucose tolerance and, as a rule, do not require antihyperglycemic therap

MODY caused by a mutation in the insulin gene

MODY10 is a rare subtype of MODY diabetes, which caused by heterozygous mutations in the insulin gene INS. There are single descriptions of families with MODY-INS or MODY10 in the literature, its clinical course is not well understood. We present a case of MODY10 in a boy with a history of diabetes mellitus (DM) in three generations (father and paternal grandmother). Proband was diagnosed with diabetes mellitus at the age of 7 years. The glycaemia at the onset of the diabetes was 10.2 mmol/l, HbA1c — 7.6%, islet cell autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADA) and islet tyrosine phosphatase 2 (IA2) antibodies (IA2) were not detected. According to the results of the oral glucose tolerance test, fasting blood glucose was 6.5 mmol/l, in 120 minutes 10.3 mmol/l, which corresponded to the diagnosis of impaired glucose tolerance. Diet with restriction of easily digestible carbohydrates was recommended, than gliclazide was added to the therapy, which the proband received for 3 years. At the age of 10, a deterioration in the parameters of carbohydrate metabolism was noted, which insulin therapy was added. Examination at the age of 12 revealed a decrease in C-peptide secretion. The child’s father has a similar phenotype — slowly progressive disorders of carbohydrate metabolism from 6 years old, from 10 years old — insulin therapy. A genetic test was provided, in the child and his father was detected a previously undescribed heterozygous mutation in the INS p.C31W. Thus, in our clinical case, MODY10 was characterized by a milder course than T1DM, but eventually leading to the development of insulin demand, which distinguishes it from the most common forms of MODY. Currently, there is no specific therapy, and the detection of a mutation in the INS gene does not affect therapeutic tactics, however, a correct genetic diagnosis makes it possible to predict the course of diabetes and provide genetic counseling to the family

Carbohydrate metabolism in children after complex treatment of medulloblastoma

BACKGROUND: Disorders of carbohydrate metabolism are frequent complications after complex treatment of cancer. Early detection of these disorders allows to modify lifestyle, if necessary, apply drug therapy and correct the identified changes in time, which will subsequently lead to a decrease in cardiovascular risks, an improvement in the quality and an increase in the life expectancy of this group of patients.AIM: To identify the frequency of occurrence and determine the optimal methods for early diagnosis of carbohydrate metabolism disorders in children after complex treatment of medulloblastoma.MATERIALS AND METHODS: 97 patients (64 boys) were examined after complex treatment of medulloblastoma (surgical treatment, craniospinal radiation therapy [CSI], chemotherapy). The median age at the time of the survey was 11.2  (5.29 -17.9) years. The average follow-up period after the end of all types of treatment is 4.7 (0.59 - 11.94) years. At the time of examination, all patients were compensated for hypothyroidism and hypocorticism (if any), and no one was on growth hormone therapy. All patients underwent a standard oral glucose tolerance test (OGTT) and determination of the level of glycated hemoglobin (HbA1c).RESULTS: None of the patients had a basal glycemic level higher than 5.5 mmol / L. Impaired glucose tolerance ( glycemia at the 120th minute ≥7.8 mmol / L <11.09 mmol / L) was detected in 10 out of 97 patients (10.3%). 7 patients with IGT had insulin resistance (according to MATSUDA index), while 1 of them had normal HOMA-IR index. Only one patient with IGT had an increase in the level of glycated hemoglobin up to 6.2%. Insulin resistance (using the MATSUDA index) was present in 30 patients, and 11 of them had a normal HOMA-IR index. Thus, 34 out of 97 patients (35.1%) had disorders of carbohydrate metabolism (IGT and / or insulin resistance). At the same time, the level of glycated hemoglobin reflected disturbances in only one case, and the basal level of glycemia was not informative in any case.CONCLUSION: Assessment of basal levels of glycemia and insulin, as well as glycated hemoglobin, is insufficient to exclude disorders of carbohydrate metabolism in patients after complex treatment of medulloblastoma. It is advisable to carry out a standard OGTT

Comparative assessment of energy metabolism, body composition and metabolic features in children with hypothalamic and simple obesity

Background: Hypothalamic obesity often develops after surgical treatment of craniopharyngioma and is characterized by rapid weight gain, high frequency of metabolic disorders, body composition specificity and resistance to standard lifestyle modification approaches and medication therapy of obesity. Recent studies show that one of the mechanisms, explaining weight gain in these children is decrease in resting energy expenditure (REE).Aims: To compare REE, body composition parameters, and the frequency of metabolic disorders in children with hypothalamic and simple obesity.Materials and methods: The study included 60 obese children aged 7 to 17 years, divided into two groups. The study group included 20 children with hypothalamic obesity, developed after craniopharyngioma treatment. The control group consisted of 40 children with simple obesity. Body composition, REE, and metabolic disorders were associated in all children.Results: Children with hypothalamic obesity showed a significant decrease of resting energy expenditure. The average decrease in REE was 13.1%, but in single patients it reached 33.4%. The percentage of fat mass in hypothalamic and simple obesity does not differ significantly (39.7% [36.2; 42.6] vs 38.8 % [35.9; 43.2]; p=0.69). Screening for metabolic disorders revealed a high prevalence of metabolic disorders in hypothalamic obesity: impaired glucose tolerance - in 10%; dyslipidemia - 55%, insulin resistance-50%, non-alcoholic fatty liver disease - 60 %.Conclusions: Children with hypothalamic obesity showed a significant decrease of resting energy expenditure. When planning a diet in this group of patients it is preferable to use indirect calorimetry. Hypothalamic obesity even at an early age is associated with a high frequency of metabolic disturbance. Hypothalamic obesity in children is not associated with more pronounced hyperinsulinemia and insulin resistance compared to the simple obesity

C-peptide levels and the prevalence of islets autoantibodies in children with type 1 diabetes mellitus with different duration of the disease

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by the development of absolute insulin deficiency. In some patients residual insulin secretion may persist for a long time. C-peptide is a widely used to measure the pancreatic beta cells function, in clinical practice and in research studies.AIM: To assess C-peptide levels and presence of islets autoantibodies (Ab) in children with different duration of T1DM and to identify factors associated with the preserved secretion.MATERIALS AND METHODS: Single-center cross-sectional study including data from 703 cases of children with T1DM, examined in the Endocrinology Research Center in 2016-2020, who was underwent a study of C-peptide levels and was positive for one or more islets antibodies (ZnT8, IA-2, GAD, ICA, IAA). There were 3 groups of patients: 1st — T1DM duration < 1 year, 2nd — from 1 to 5 years, 3rd — > 5 years.RESULTS: The median of the fasting C-peptide level in the 1st group was 0.6 ng/ml [0.27; 1.09]; in the 2nd group — 0.2 ng/ml [0.01; 0.8]; in the 3rd group — 0.01 ng/ml [0.01; 0.037]. The preserved secretion of C-peptide (> 0.6 ng/ml) was determined in 51.4% in the 1st group, in 31.4% — in the 2nd group and in 11.4% in the 3rd group. In patients with obesity during the first year from the T1DM diagnosis C-peptide levels above 1.1 ng/ml was determined significantly more often (65.2%), as well as at the period of 1 to 5 years of the disease (35.7%), compared with children with normal BMI (18.5% and 14.5%, respectively) or overweight (15.7% and 19%, respectively), p <0.01. A negative correlation was found between C-peptide levels and the duration of T1DM (r = -0.489, p = 0.000), the daily dose of insulin (r = -0.637, p = 0.000), a positive association was found with the age of diagnosis of T1DM (r = 0.547, p = 0.000). The frequency of the presence of one type of islets autoantibodies in all groups was 29.5%, 2 types — 33.6%, 3 and more types — 36.9%. The titer of IA-2, ZnT8 decreased with the disease duration (p <0.05 and p <0.01, respectively), while the titer of ICA increased (p <0.01). No associations between the types, number, antibodies titer and C-peptide levels, age of disease manifestation were found.CONCLUSION: C-peptide levels in children with T1DM in groups with older age at diagnosis and with obesity is significantly higher for the first 5 years of the disease. The study have shown the titer of IA-2, ZnT8 is decreasing with the disease duration, in turn, the frequency of detection of ICA increases. No association between C-peptide levels and the type, number and titer of antibodies were found

The role of specific pancreatic antibodies in the differential diagnosis of complete clinical and laboratory remission of type 1 diabetes mellitus and MODY in children

BACKGROUND: T1D is characterized by autoimmune destruction of pancreatic β-cells, which develops due to genetic and environmental risk factors. Shortly after initiating the treatment with insulin, 80% of children with T1D may require smaller doses of insulin and develop clinical and laboratory remission of the disease so called «honeymoon». The issue of whether there is a need of differential diagnosis between autoimmune DM and non-immune forms of DM raises in cases of preclinical diagnosis of T1D and laboratory remission for more than 6 months.AIM: To study the clinical, immunological, genetic characteristics of T1D remission phase and MODY in children, to determine the diagnostic criteria for T1D and MODY in children.MATERIALS AND METHODS: A single-centre, cross sectional noncontrolled comparative study of two independent cohorts. Data of 150 children examined in the Endocrinology Research Center (January 2016–June 2021). First cohort included patients with complete clinical and laboratory remission of T1D (n=36), second cohort included patients with MODY, confirmed by genetic study (n=114).RESULTS: The median age of diabetes manifestation was significantly higher in patients with T1D — 11.25 years [8.33; 13.78] than in patients with MODY — 7.5 years [4.6; 12.2] (p=0.004). In patients with T1D remission the level of glycated hemoglobin was 6.0% [5.6; 6.4], in group with MODY — 6.5% [6.2; 6.7] (p<0.001). Patients with monogenic diabetes had impaired fasting glucose — 6.27 mmol/l [5.38; 6.72], while patients with remission phase had normoglycemia — 5.12 mmol/l [4.17; 5.87]. The oral glucose tolerance test was perform to all patients, two-hour glucose level did not significantly differ in two groups (p=0.08). A strong family history of diabetes in patients with MODY registered more often (93% vs. 66.7%). A positive autoantibody titer detected more often in patients with remission of T1D (77.8%) than in patients with MODY (11.4%). In addition, no more than 1 type of autoantibodies was detected in patients with MODY.CONCLUSION: Antibodies ZnT8 and IA2 showed the greatest significance for the differential diagnosis of T1D and MODY in cases with long absents of insulin requirement in children with diabetes mellitus. Genetic test is recommended in seronegative cases. If only one type of AT is detected, specialist should decide on the need to do diagnostic genetic test based on a comprehensive analysis of the patient’s clinic characteristics, including family history, manifestation and blood glucose levels