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1.
Eur J Pediatr ; 176(6): 713-722, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28382540

ABSTRACT

In this study, we compare the prevalence of alcohol and cigarette use among Polish adolescents with type 1 diabetes mellitus (T1DM) (n = 209), aged 15-18 years, with that of a large cohort of their healthy peers, using standardized questionnaire used in the European School Survey Project on Alcohol and Drugs (ESPAD). The lifetime, previous year, and past 30-day prevalence of alcohol consumption was high among adolescents with T1DM but lower than in the controls (82.8 vs 92.0%, 71.7 vs 85.6%, and 47.5 vs 69.7%, respectively, p < 10-5). The lifetime and 30-day prevalence of cigarette use was also lower among patients than the controls (54.6 vs 65.5%, p = 0.001 and 27.3 vs 35.9%, p = 0.012, respectively). Patients who admitted smoking exhibited worse metabolic control than non-smokers (p < 0.0001) and had a higher chance of developing diabetic ketoacidosis. The incidence of severe hypoglycemia was higher among those who reported getting drunk in the previous 30 days (p = 0.04) and lifetime smoking (p = 0.01). CONCLUSIONS: Although alcohol and cigarette consumption is lower than in controls, it is common among teenagers with type 1 diabetes, effecting metabolic control and causing the risk of acute diabetes complications. Better prevention strategies should be implemented in this group of patients in their early teen years. What is Known: • Substance use remains a significant cause of morbidity and mortality among teenagers with type 1 diabetes. • Current medical literature contains inconsistent data on the prevalence of alcohol and cigarette use among adolescents with type 1 diabetes, mostly due to methodological problems with conducting such surveys. What is New: • Methodological approach: we used a validated questionnaire from the European School Survey Project on Alcohol and Other Drugs (ESPAD) and compared the results to a large national control group of 12,114 healthy students who took part in ESPAD in 2011.


Subject(s)
Adolescent Behavior , Alcohol Drinking/epidemiology , Diabetes Mellitus, Type 1/psychology , Smoking/epidemiology , Adolescent , Alcohol Drinking/adverse effects , Case-Control Studies , Diabetes Mellitus, Type 1/physiopathology , Female , Health Surveys , Humans , Male , Poland/epidemiology , Prevalence , Smoking/adverse effects
2.
Diabetes Care ; 36(8): 2311-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23462667

ABSTRACT

OBJECTIVE: Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide. RESEARCH DESIGN AND METHODS: To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5'-triphosphate inhibition were associated with the most severe neurologic symptoms. CONCLUSIONS: We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.


Subject(s)
Cerebellum/metabolism , Diabetes Mellitus/drug therapy , Potassium Channels, Inwardly Rectifying/genetics , Sulfonylurea Compounds/therapeutic use , Adolescent , Cerebellum/blood supply , Cerebellum/drug effects , Child , Child, Preschool , Female , Glyburide/therapeutic use , Humans , Infant , Infant, Newborn , Male , Potassium Channels, Inwardly Rectifying/biosynthesis , Tomography, Emission-Computed, Single-Photon
3.
Pediatr Diabetes ; 12(4 Pt 2): 424-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21447088

ABSTRACT

BACKGROUND: Behavioral problems are an issue among adolescents with type 1 diabetes (T1D). The authors hypothesize that theft, possibly because of an underlying psychiatric morbidity, may be a way of procuring sweets leading to worse glycemic control. OBJECTIVE: To evaluate psychiatric morbidity and the association of theft and metabolic control among children and adolescents with T1D, using data from an interim analysis of an ongoing quality-of-life and psychiatric comorbidity study. METHODS: One hundred and nine consecutively hospitalized individuals aged 8-18 years with T1D were asked about incidents of theft. The data on psychiatric morbidity were taken from an ongoing longitudinal study using semi-structured diagnostic interview (KSADS-PL). RESULTS: Overall, 10 children (9%) reported that they had committed theft. Primary motivation for theft was reported as either direct or indirect gain of sweets. Patients who admitted to theft were more likely to have worse metabolic control expressed by glycated hemoglobin (HbA1c) [10.4% (interquartile range 9.8-11.8) vs. 7.7% (6.9-8.8); p < 0.0001] and higher odds of having psychiatric morbidity (odds ratio 8.2; 95% confidence interval 1.9-34.2) than their peers. In the subgroup analysis of patients with psychiatric morbidity, HbA1c was significantly higher if having committed a theft was reported [10.2% (9.4-11.9) vs. 8.1% (7.2-9.2); p < 0.001]. No significant differences in socioeconomic status, clinical factors, or rates of complications were found. CONCLUSIONS: Theft may be a factor negatively affecting metabolic control in children with T1D and underlying psychiatric co-morbidity. Psychiatric morbidity is more frequent among patients with T1D and a history of theft.


Subject(s)
Diabetes Mellitus, Type 1/psychology , Theft , Adolescent , Child , Comorbidity , Diabetes Mellitus, Type 1/therapy , Female , Glycated Hemoglobin/metabolism , Humans , Male , Mental Disorders/psychology , Motivation
4.
Proc Natl Acad Sci U S A ; 106(34): 14460-5, 2009 Aug 25.
Article in English | MEDLINE | ID: mdl-19667185

ABSTRACT

Maturity-onset diabetes of the young (MODY) is a subtype of diabetes defined by an autosomal pattern of inheritance and a young age at onset, often before age 25. MODY is genetically heterogeneous, with 8 distinct MODY genes identified to date and more believed to exist. We resequenced 732 kb of genomic sequence at 8p23 in 6 MODY families unlinked to known MODY genes that showed evidence of linkage at that location. Of the 410 sequence differences that we identified, 5 had a frequency <1% in the general population and segregated with diabetes in 3 of the families, including the 2 showing the strongest support for linkage at this location. The 5 mutations were all placed within 100 kb corresponding to the BLK gene. One resulted in an Ala71Thr substitution; the other 4 were noncoding and determined decreased in vitro promoter activity in reporter gene experiments. We found that BLK--a nonreceptor tyrosine-kinase of the src family of proto-oncogenes--is expressed in beta-cells where it enhances insulin synthesis and secretion in response to glucose by up-regulating transcription factors Pdx1 and Nkx6.1. These actions are greatly attenuated by the Ala71Thr mutation. These findings point to BLK as a previously unrecognized modulator of beta-cell function, the deficit of which may lead to the development of diabetes.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Insulin-Secreting Cells/metabolism , Mutation , src-Family Kinases/genetics , Adolescent , Adult , Animals , Blotting, Western , Cell Line, Tumor , DNA Mutational Analysis , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Family Health , Female , Genetic Predisposition to Disease , Humans , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/pathology , Luciferases/genetics , Luciferases/metabolism , Male , Microscopy, Confocal , Middle Aged , Pedigree , RNA Interference , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Young Adult , src-Family Kinases/metabolism
6.
Diabetes ; 54(11): 3331-5, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16249462

ABSTRACT

Chemokines and their receptors have been implicated in the development of diabetic nephropathy. To determine whether the risk of diabetic nephropathy is influenced by two functional polymorphisms in the regulated upon activation normal T-cell expressed and secreted (RANTES) receptor gene (CCR5), we recruited patients with type 1 diabetes, including 496 case subjects with overt proteinuria or end-stage renal disease and 298 control subjects with normoalbuminuria. Male carriers of the 59029G allele, which is associated with diminished expression of CCR5 on the surface of immunocompetent cells, had significantly higher risk of developing diabetic nephropathy than noncarriers (OR [95% CI] 1.9 [1.2-3.0]). Similarly, male carriers of the 32-bp deletion, which causes truncation of the protein, had significantly higher risk of diabetic nephropathy than noncarriers (2.3 [1.3-4.2]). Combining both polymorphisms, three haplotypes were distinguished: one nonrisk haplotype carrying the 59029A allele and the 32-bp insertion and two risk haplotypes carrying the 59029A allele with the 32-bp deletion and carrying the 59029G allele with the 32-bp insertion. The distribution of these haplotypes differed significantly (P < 0.00001) in men with and without diabetic nephropathy but was not associated with diabetic nephropathy in women. In conclusion, two functional polymorphisms in CCR5 that decrease expression of the RANTES receptor on immunocompetent cells are associated with increased risk of diabetic nephropathy in type 1 diabetes, but only in men.


Subject(s)
Chemokine CCL5/metabolism , Diabetes Mellitus, Type 1/genetics , Diabetic Nephropathies/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Receptors, CCR5/genetics , Sex Characteristics , Adult , Diabetes Mellitus, Type 1/complications , Diabetic Nephropathies/complications , Female , Genotype , Humans , Male , Middle Aged
7.
Diabetes ; 53(2): 486-91, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14747302

ABSTRACT

In a panel of large Caucasian pedigrees, we genotyped markers in eight chromosomal regions previously reported as supporting linkage with type 2 diabetes. We previously reported significant linkage on chromosome 20q (maximum logarithm of odds score [MLS] = 2.79) in this panel. In the present analysis, candidate regions on 1q, 2q, 3q, 5q, 9q, and 10q yielded little evidence for linkage; a region on 2p (MLS = 1.64, P = 0.01 at position 9.0 cM) gave suggestive evidence of linkage; and a region on 8p (MLS = 3.67, P = 2.8 x 10(-5), at position 7.6 cM) gave significant evidence of linkage. Conditional analyses were performed for both 2p and 8p regions and the region reported on 20q. The MLS for 2p increased from 1.64 to 1.79 (empirical P = 0.142) when conditioned for heterogeneity on 20q. The case was similar for 8p, where the MLS increased from 3.67 to 4.51 (empirical P = 0.023) when conditioned on families without evidence of linkage at 20q. In conclusion, our data support a type 2 diabetes susceptibility locus on chromosome 8p that appears to be independent from other susceptibility loci. Although we were able to replicate linkage in our pedigrees on chromosome 2p, we did not find evidence of linkage for regions on 1q, 2q, 3q, 5q, 9q, or 10q.


Subject(s)
Chromosomes, Human, Pair 8/genetics , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease/genetics , Age of Onset , Body Weight , Chromosome Mapping/methods , Genetic Linkage/genetics , Humans , Middle Aged , Odds Ratio
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