Phenotype variability and neonatal diabetes in a large family with heterozygous mutation of the glucokinase gene

Monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY) is usually characterized by a mild clinical phenotype. The clinical course of diabetes may be, however, highly variable. The authors present a child with diabetes manifesting with ketoacidosis during the neonatal period, born in a large family with ten members bearing a heterozygous p.Gly223Ser mutation in GCK. DNA sequencing and multiplex ligation-dependent probe amplification were used to confirm GCK mutation and exclude other de novo mutations in other known genes associated with monogenic diabetes. Continuous glucose monitoring (CGM) was used to assess daily glycemic profiles. At the onset of diabetes the child had hyperglycemia 765 mg/dl with pH 7.09. Her glycated hemoglobin level was 8.6% (70.5 mmol/mol). The C-peptide level was below normal range (<0.5 pmol/ml) at onset, and the three- and 6-month follow-up examinations. Current evaluation at age 3 still showed unsatisfactory metabolic control with HbA1c level equal to 8.1% (65.0 mmol/mol). CGM data showed glucose concentrations profile similar to poorly controlled type 1 diabetes. The patient was confirmed to be heterozygous for the p.Gly223Ser mutation and did not show any point mutations or deletions within other monogenic diabetes genes. Other family members with p.Gly223Ser mutation had retained C-peptide levels and mild diabetes manageable with diet (five individuals), oral hypoglycemizing agents (five patients), or insulin (one patient). This mutation was absent within all healthy family members. Heterozygous mutations of the GCK gene may result in neonatal diabetes similar to type 1 diabetes, the cause of such phenotype variety is still unknown. The possibility of other additional, unknown mutations seems to be the most likely explanation for the unusual presentation of GCK-MODY

Efficacy and safety of insulin pump treatment in adult T1DM patients : influence of age and social environment

Introduction and objective. Continuous subcutaneous insulin infusion (CSII) via personal insulin pump is a valuable therapeutic tool in T1DM patients. However, adherence to recommended CSII- related behaviours may be of concern to young adults with intensive, variable daily activities (students, young professionals). The aim of this observational study was to estimate treatment outcomes in young adult patients with T1DM, and compare them with older individuals. Materials and methods. Overall, 140 adults with T1DM on CSII were examined, divided into 2 subgroups: 77 patients younger than 26 years of age (mean 20.6 years) and 63 older subjects (mean 39.0). We compared the glycaemic control in both groups of T1DM subjects and analyzed treatment attitudes to identify potentially modifiable behaviours influencing the efficacy of the treatment. Results. The younger individuals were characterized by significantly worse treatment outcomes, compared to the older ones: the mean HbA1c levels were 7.6 ± 1.3% and 6.9±1.3% (p=0.00001), while the mean glucose levels based on glucometer downloads were 161±33.6 mg/dL and 136±21.8 mg/dL (p=0.00001), respectively. The frequency of self-monitoring of blood glucose (SMBG) was lower in younger individuals (5.3±2.1 vs. 7.0±2.8 daily, p=0.0005, respectively); they were also less frequently used advanced pump functions, e.g. the bolus calculator (48% vs. 67% users, p=0.0014, respectively). Conclusions. The efficacy of CSII treatment observed in young T1DM adults was worse than in older patients. The reason for this phenomenon remains unclear, it may be due simply to age-dependend behaviours, to social environment, or both

GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus

Background: The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients.&lt;p&gt;&lt;/p&gt; Methods: Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA).&lt;p&gt;&lt;/p&gt; Results: Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables.&lt;p&gt;&lt;/p&gt; Conclusions: Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients

Podaż węglowodanów w diecie i kontrola glikemii u pacjentów leczonych za pomocą mieszanek insuliny ludzkiej

  Introduction. The treatment with pre-mixed human insulins (PMHI) is globally one of the most popular models of insulin therapy. Achieving good glycaemic control on PMHI may, however, be difficult, mostly due to inconsistent calorie and carbohydrate intake. The aim of the study was to examine the impact of dietary modification on glucose levels in patients with type 2 diabetes mellitus (T2DM) treated with PMHI. Materials and methods. In this prospective cross-over analysis we studied 8 T2DM PMHI treated individuals (mean HbA1c 8.4%). We exposed patients to 2 diets, both based on steady calorie/carbohydrate content: „A” — 50% calories from carbohydrates, 30% from fat, 20% from protein, „B”— 40% from carbohydrates, 30% from fat and 30% from protein. The study was performed in home settings, all the meals were delivered to the patients. Each patient was exposed to diet A for 9 days, than after 7 days of wash-out to 9 days of diet B. Glucose patterns were assessed with continuous glucose monitoring system (CGMS, iPro, Medtronic, USA). Results. Switching from diet A to diet B resulted in a decrease in mean glucose levels (CGMS data) from 145 mg/dL to 133 mg/dL (p = 0.0001), SD reduction from 51 to 42 mg/dL (p = 0.0429), and a decrease in time spent above the target of 180 mg/dL from 18% to 11% (p = 0.0006). Conclusions. The study demonstrates that consistent and repeatable carbohydrate (CH) and calorie intake with moderate restriction of CHs helps to improve glycaemic control in this group of patients.    Wstęp. Leczenie mieszankami insuliny ludzkiej (PMHI, pre-mixed human insulin) jest na całym świecie jednym z najpopularniejszych modeli insulinoterapii. Jednak osiągnięcie dobrej kontroli glikemii u osób stosujących PMHI może być trudne, głównie ze względu na zmienne spożycie węglowodanów i podaż kalorii. Badanie przeprowadzono w celu oceny wpływu modyfikacji diety na stężenia glukozy u chorych na cukrzycę typu 2 (T2DM, type 2 diabetes mellitus) stosujących PMHI. Materiał i metody. Do tego prospektywnego badania przeprowadzonego w układzie naprzemiennym włączono 8 chorych na T2DM leczonych PMHI (średnie stężenie HbA1c 8,4%). U chorych zastosowano 2 diety, obie cechujące się stałą zawartością kalorii/węglowodanów: dieta A — 50% kalorii pochodzi z węglowodanów, 30% — z tłuszczów, 20% — z białek; dieta B — 40% kalorii pochodzi z węglowodanów, 30% — z tłuszczów i 30% — z protein. Badanie prowadzono w warunkach domowych, dostarczano chorym wszystkie posiłki. Każdy chory stosował dietę A przez 9 dni, a następnie po 7-dniowym okresie wypłukiwania przez 9 dni stosował dietę B. Profile glukozy oceniano przy użyciu systemu ciągłego monitorowania glikemii (CGMS, continuous glucose monitoring system, iPro, Medtronic, USA). Wyniki. Zmiana z diety A na dietę B spowodowała zmniejszenie średnich stężeń glukozy (dane z system CGMS) ze 145 mg/dl do 133 mg/dl (p = 0,0001), redukcję SD z 51 do 42 mg/dl (p = 0,0429) oraz skrócenie czasu, w którym glikemia utrzymywała się powyżej progowej wartości 180 mg/dl z 18% do 11% (p = 0,0006). Wnioski. W badaniu wykazano, że zapewnienie odpowiedniej i powtarzalnej podaży węglowodanów i kalorii z umiarkowanym ograniczeniem węglowodanów umożliwia poprawę kontroli glikemii u chorych na cukrzycę typu 2.

Diabetes as a risk factor of death in hospitalized COVID-19 patients – an analysis of a National Hospitalization Database from Poland, 2020

IntroductionDiabetes is one of the comorbidities associated with poor prognosis in hospitalized COVID-19 patients. In this nationwide retrospective study, we evaluated the risk of in-hospital death attributed to diabetes.MethodsWe analyzed data from discharge reports of patients hospitalized with COVID-19 in 2020 as submitted to the Polish National Health Fund. Several multivariate logistic regression models were used. In each model, in-hospital death was estimated with explanatory variables. Models were built either on the whole cohorts or cohorts matched with propensity score matching (PSM). The models examined either the main effects of diabetes itself or the interaction of diabetes with other variables.ResultsWe included 174,621 patients with COVID-19 who were hospitalized in the year 2020. Among them, there were 40,168 diabetic patients (DPs), and the proportion of DPs in this group was higher than in the general population (23.0% vs. 9.5%, p&lt;0.001). In this group of COVID-19 hospitalizations, 17,438 in-hospital deaths were recorded, and the mortality was higher among DPs than non-diabetics (16.3% vs. 8.1%, p&lt;0.001). Multivariate logistic regressions showed that diabetes was a risk factor of death, regardless of sex and age. In the main effect analysis, odds of in-hospital death were higher by 28.3% for DPs than for non-diabetic patients. Similarly, PSM analysis including 101,578 patients, of whom 19,050 had diabetes, showed that the risk of death was higher in DPs regardless of sex with odds higher by 34.9%. The impact of diabetes differed among age groups and was the highest for patients aged 60-69.ConclusionsThis nationwide study confirmed that diabetes was an independent risk factor of in-hospital death in the course of COVID-19 infection. However, the relative risk differed across the age groups

Continuous glucose monitoring and insulin pump therapy in pregnant women with type 1 diabetes mellitus

Objectives: We examined the impact of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring systems (CGM) during pregnancy in women with pre-gestational type 1 diabetes (T1DM) on glycemic control and subsequent adverse outcomes.Material and methods: In this observational, one-center study we analyzed records of consecutive 109 T1DM pregnancies (2016–2017). The final analyzed group consisted of 81 singleton pregnancies who met inclusion and exclusion criteria. We searched for the association between the use of CSII with or without CGM and pregnancy planning with glycated hemoglobin A1c (HbA1c) through pregnancy and after delivery as well as maternal and infant outcomes.Results: Patients using CSII and CGM vs CSII without CGM and MDI (multiple daily injections) users had the lowest HbA1c levels during and after pregnancy (5.3%, 5.3%, 5.2% and 5,5% in the 1st, 2nd, 3rd trimester and postpartum visit, p = 0.003, p = 0.030, p = 0.039 and p = 0.002, respectively). Patients treated with insulin pumps with CGM and additional functions of automatic insulin delivery suspension on low glucose level (SLG) or predictive low glucose suspend (PLGS) during the third trimester and after pregnancy achieved a significantly lower HbA1c than the other CSII patients. We did not find any differences between the study groups in gestational age at delivery, preterm births, birth weight or macrosomia risk. Despite very good glycemic control, the risk of macrosomia remained high (19.7%).Conclusions: The use of pumps equipped with CGM, especially with automatic insulin delivery suspension, may improve glycemic control in pregnant T1DM women. The proportion of macrosomia remained high

Increased nitric oxide availability attenuates high fat diet metabolic alterations and gene expression associated with insulin resistance

<p>Abstract</p> <p>Background</p> <p>High fat diet impairs nitric oxide (NO) bioavailability, and induces insulin resistance. The link between NO availability and the metabolic adaptation to a high fat diet is not well characterized. The purpose of this study was to investigate the effect of high fat diet on metabolism in mice with decreased (eNOS-/-) and increased (DDAH overexpressed) NO bioavailability.</p> <p>Methods</p> <p>eNOS-/- (n = 16), DDAH (n = 24), and WT (n = 19) mice were fed a high fat diet (HFD) for 13 weeks. Body weight, biochemical parameters, adipokines and insulin were monitored. The matrigel <it>in vivo </it>model with CD31 immunostaining was used to assess angiogenesis.</p> <p>Gene expression in adipose tissues was analyzed by microarray and Real Time PCR. Comparisons of the mean values were made using the unpaired Student t test and p < 0.05 were considered statistically significant.</p> <p>Results</p> <p>eNOS-/- mice gained less weight than control WT and DDAH mice. In DDAH mice, a greater increase in serum adiponectin and a lesser increment in glucose level was observed. Fasting insulin and cholesterol levels remained unchanged. The angiogenic response was increased in DDAH mice. In adipose tissue of DDAH mice, genes characteristic of differentiated adipocytes were down-regulated, whereas in eNOS-/- mice, genes associated with adipogenesis, fatty acid and triglyceride synthesis were upregulated.</p> <p>Conclusions</p> <p>Our results indicate that increased NO availability attenuates some HFD induced alterations in metabolism and gene expression associated with insulin resistance.</p

Quality of life in the course of a one-year use of an advanced hybrid closed-loop system in adults with type 1 diabetes previously naïve to advanced diabetes technology

AimTo evaluate the effect of a one-year use of an advanced hybrid closed-loop (AHCL) system on the quality of life, level of anxiety, and level of self-efficacy in adults with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI) and naïve to advanced diabetes technologyMethodsA total of 18 participants of a previously published 3-month randomized trial (10 men, 8 women; age 40.9 ± 7.6 years) who were switched directly from MDI/BMG to AHCL completed 12 months of MiniMed 780G™system use (a 3-month randomized trial followed by a 9-month follow-up phase). At month 6 of the study, patients were switched from the sensor GS3 (Continuous Glucose Monitoring) system, powered by Guardian™ Sensor 3) to GS4. Quality of life was assessed using the Polish validated version of the ‘QoL-Q Diabetes’ questionnaire. The level of anxiety was evaluated with the use of the State-Trait Anxiety Inventory (STAI). Self-efficacy was assessed with the General Self-Efficacy Scale (GSES). Results were obtained at baseline and at the end of the study.ResultsSignificant increase in QoL was reported in the global score (p=0.02, Cohen d=0.61) and in as many as 11 out of 23 analyzed areas of life: being physically active (p=0.02, Cohen d = 0.71); feeling well (p&lt;.01, Cohen d = 0.73); feeling in control of my body (p&lt;.01, Cohen d = 0.72); looking good (p&lt;.01, Cohen d = 1.07); working (p&lt;.01, Cohen d = 1.12); sleeping (p=0.01, Cohen d = 0.66); eating as I would like (p&lt;.01, Cohen d = 0.79); looking after or being useful to others (p= 0.02, Cohen d = 0.65); being active with pets/animals (p&lt;.01, Cohen d = 0.95); being spontaneous (p=0.02, Cohen d = 0.67); and doing “normal” things (p=0.02, Cohen d = 0.67). Both state (p=0.04, Cohen d = 0.56) and trait (p=0.02, Cohen d = 0.60) anxiety decreased while the general self-efficacy increased (p=0.03, Cohen d = 0.76). No participant stopped the use of the pump.ConclusionAdult patients with T1D previously treated with MDI and naïve to modern technologies experienced significant improvement in their psychological well-being after transitioning to the AHCL system after 12 months of treatment