Rising incidence of type 1 diabetes mellitus in children and adolescents in Cyprus in 2000-2004

Introduction:  The incidence of type 1 diabetes mellitus (T1DM) has dramatically increased recently in some countries.
Aim:  To ascertain any changes in the incidence of T1DM in our population during the years 1990–2004.
Methodology:  All newly diagnosed cases of T1DM children under the age of 15 yr were registered and relevant information was obtained. Population demographic data based on the most recent census were used for calculations.
Results:  The overall mean annual incidence of T1DM during this 15-yr period was 11.9/100 000 person-years, with a statistically significant increase in the third 5-yr period (14.9/100 000 person-years).
The incidence during the first (1990–1994) and second (1995–1999) 5-yr periods was 10.5/100 000 person-years (p < 0.001). The overall male:female ratio was 0.94. Seasonal distribution for the first and second 5-yr periods revealed a higher incidence during winter and autumn months. Seasonal variation, however, disappears in the third 5-yr period, where no differences were found between the four seasons.
Conclusion:  The incidence of newly diagnosed T1DM cases has increased during 2000–2004. A seasonal variation during the first and second 5-yr periods was no longer observed in the third 5-yr period.     

HLA-DRB1*08 allele may help to distinguish between type 1 diabetes mellitus and type 2 diabetes mellitus in Mexican children

BACKGROUND: It may be difficult to distinguish type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) in the pediatric population. Autoantibodies may help to differentiate both types of diabetes, but sometimes these are positive in patients with T2DM and negative in patients with T1DM. The human leukocyte antigen (HLA)-DR genotype has been associated with T1DM and with T2DM only in adults and in determined cases. AIM: To determine the differences in HLA class II allele frequencies in Mexican children with T1DM and T2DM. METHODS: We included 72 children with T1DM, 28 children with T2DM, and 99 healthy controls. All were Mexican, and diabetes was diagnosed according to the clinical and laboratory criteria established by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. The HLA-DRB1 typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe and polymerase chain reaction sequence-specific primers. RESULTS: We found an increased frequency of HLA-DRB1*08 and a decreased frequency of HLA-DRB1*04 in the group with T2DM vs. T1DM [p = 0.0001, odds ratio (OR) = 10.58, 95% confidence interval (CI) = 3-40.8 and p = 0.0006, OR = 0.24, 95% CI = 0.11-0.53, respectively]. No significant differences were found between HLA-DRB1 alleles in T2DM vs. controls. In the group with T1DM, there was a significantly increased frequency of the HLA-DR4 and HLA-DR3 alleles relative to controls (p = 0.0000001, OR = 3.59, 95% CI = 2.2-5.8 and p = 0.00009, OR = 4.66, 95% CI = 2.1-10.3, respectively). CONCLUSION: There are significant differences in the HLA profile in Mexican children with T1DM and T2DM. HLA typing could play a role in the differentiation between both types of diabetes in this population.     

Onset of type 1 diabetes mellitus in two patients with maturity onset diabetes of the young

The association between maturity onset diabetes of the young (MODY) and type 1 diabetes mellitus (T1DM) has been rarely described. We report two patients affected by MODY who developed T1DM. Case 1: a 4-yr-old girl referred for glycosuria presented hemoglobin A1c (HbA1c) of 6.6%. Islet cell antibodies (ICA) and anti-glutamic acid decarboxylase (GADA) were initially negative. As her father, uncle and grandmother showed mild hyperglycemia, they were screened for MODY 2. A novel mutation in glucokinase gene was found in the family. Few months later, her glycemic control worsened consistently and she required insulin treatment. A high titer of GADA and ICA was then detected. Six years afterwards insulin requirement is 0.8 U/kg and HbA1c 6.7%. Case 2: a 15-yr-old boy treated for growth hormone deficiency was found with a blood glucose level of 106 mg/dL. HbA1c was 7.2%, ICA and GADA were negative. Family history was positive for autoimmune diseases and type 2 diabetes mellitus. The patient was investigated for MODY 2 and MODY 3, and a mutation of hepatocyte nuclear factor-1 alpha gene was found. The same mutation was found in the mother who had never been referred for hyperglycemia. After 1 yr, due to an unjustified worsening of the metabolic control, autoimmunity was again investigated and a mild positivity was found. He then required insulin therapy and after 5 yr current HbA1c was 8.2%. The diagnosis of MODY does not exclude the risk of developing T1DM. Therefore autoimmunity should be investigated when ordinary treatments fail and metabolic control unexpectedly worsens.     

Microalbuminuria and abnormal ambulatory blood pressure in adolescents with type 2 diabetes mellitus

OBJECTIVE: To determine whether risk factors for cardiovascular disease and diabetic nephropathy, as evidenced by abnormalities of ambulatory blood pressure (ABP), dyslipidemia, and microalbuminuria (MA), are present in adolescents with type 2 diabetes mellitus (T2DM). STUDY DESIGN: We enrolled 26 minority adolescents recently diagnosed with T2DM and 13 obese control subjects without diabetes mellitus. ABP monitoring was performed, and a 24-hour urine, a fasting lipid profile, blood urea nitrogen, creatinine, homocysteine, and hemoglobin A 1 c levels were obtained. The patients with T2DM underwent echocardiograms. RESULTS: Forty percent of the patients with T2DM had MA (> or = 30 mg of microalbumin/day), compared with none of the control subjects ( P < .05). There were no significant differences between patients with T2DM who had MA and patients with T2DM who didn't have MA in demographics, characteristics, casual BP, echocardiographic findings, and hemoglobin A 1 c levels. Average daytime systolic BP was greater in patients with T2DM with MA than patients without MA (129 versus 121 mm Hg, P = .03) and compared with the control subjects (113 mm Hg, P = .01). Patients with MA had an average daytime systolic BP load that was higher than patients without MA (37.1 versus 5.1%, P = .008) and compared with the control subjects (2.6%, P < .001). CONCLUSION: As in adults, adolescents with T2DM exhibit abnormalities of ABP, dyslipidemia, and microalbuminuria.     

应用胰岛素泵治疗儿童及青少年1型糖尿病对糖代谢的影响

为观察应用胰岛素泵治疗儿童及青少年1型糖尿病(T1DM)对糖代谢的影响 ,随访10例胰岛素泵治疗的T1DM患儿 ,分别观察胰岛素泵治疗前、后6个月的糖化血红蛋白值(HbA1c)、胰岛素用量、严重低血糖及酮症酸中毒发生次数的变化情况。结果显示 ,胰岛素泵治疗6个月后HbA1c 显著下降 ,治疗前为8.97 %±1.69 %,治疗后为7.51 %±1.17 % (t=2.52 ,P<0.05) ;胰岛素用量无显著下降 ;未发生严重低血糖和酮症酸中毒。表明胰岛素泵治疗可有效控制血糖 ,明显降低HbA1c,减少低血糖及酮症酸中毒的发生 ,是儿童及青少年T1DM常规治疗的较好选择。     

The effects of metabolic control on oxidized low-density lipoprotein antibodies in children and adolescents with type 1 diabetes mellitus

OBJECTIVE: To assess the oxidized low-density lipoprotein (oxLDL) antibody status in childhood type 1 diabetes mellitus (T1DM) and to investigate the effect of metabolic control on the oxLDL antibodies. SUBJECTS AND METHODS: The study included 36 T1DM patients (aged 6.6-18.1 yr) and 20 age- and sex-matched healthy subjects. Serum levels of oxLDL antibodies, lipids, and hemoglobin A1c (HbA1c) were measured. The patients with diabetes were divided into two groups according to their metabolic control levels. Group I (the patient group with good or fairly good metabolic control, n = 21) and group II (the patient group with poor metabolic control, n = 15) included children with diabetes having an actual HbA1c levels of < or = 9 and >9%, respectively. RESULTS: The oxLDL antibody level was higher in T1DM patients than in control subjects [278 (37-1289) vs. 110 (37-235) mU/mL] (p < 0.001). The patients with diabetes in group I had higher antibody levels against oxLDL [488 (51-1289) mU/mL] than both those in group II [183 (37-1207) mU/mL] and control group [110 (37-235) mU/mL] (p < 0.001). oxLDL antibodies were inversely correlated with actual HbA1c levels (r = -0.42, p = 0.01). CONCLUSIONS: Increased levels of oxLDL antibodies in pediatric patients indicate that the increased lipid peroxidation in T1DM begins in childhood. oxLDL antibody levels are inversely correlated with actual HbA1c levels in children with diabetes, as shown in adult patients. As metabolic control worsens, the free oxLDL antibody levels decrease perhaps because of immune complex formation and the atherosclerosis risk increases. The risk may be diminished by improving metabolic control as reflected in the correlation between current HbA1c and oxLDL levels.     

Glycemic control in adolescents with type 1 diabetes mellitus improves lipid serum levels and oxidative stress

Introduction:  Atherosclerosis begins in childhood, and diabetes is a risk factor for coronary heart disease. Dyslipidemia is prevalent in children with type 1 diabetes mellitus (T1DM), with an association between elevated hemoglobin A1c (HbA1c), serum lipid levels, and oxidative stress. Our aim was to examine the effect of metabolic control on serum lipid levels and oxidative stress in adolescents with T1DM.
Methods:  Twenty-six adolescents (13 boys and 13 girls), aged 15.65 ± 1.5 yr, with disease duration of 5.9 ± 2.8 yr and average HbA1c 10.8 ± 1.9% were assigned to intensive insulin therapy for 3 months. Comparisons for HbA1c, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, total triglycerides (TG), total cholesterol (TC), apolipoprotein AI, apolipoprotein AII, apolipoprotein B (ApoB), and thiobarbituric acid reactive substances (TBARS) were done between patients whose HbA1c improved by 0.5% or more (GR1) and the rest of the cohort (patients whose HbA1c improved by <0.5%, did not change, or increased) (GR2).
Results:  ApoB (p = 0.047) and TBARS (p = 0.01) were significantly lower at the end of the study in GR1. In GR2, TC (p = 0.01) and LDL (p = 0.03) were significantly higher at study end. Overall, significant beneficial changes in TC (p = 0.006), TG (p = 0.04), LDL (p = 0.02), ApoB (p = 0.015), and oxidative stress (p = 0.001) were found in GR1 compared with GR2.
Conclusions:  We provide direct evidence for the beneficial effect of tight metabolic control on serum lipids and oxidative stress in adolescents with T1DM, indicating that tight metabolic control may reduce cardiovascular risk in these patients.     

儿童和青少年1型糖尿病流行病学及治疗研究进展

1型糖尿病作为儿童和青少年糖尿病的主要类型,近20年来发病率有明显的增加趋势,引起全世界越来越多的关注.该文综述了近年来国内外儿童和青少年1型糖尿病流行病学、治疗和管理方面的研究进展,通过对比国内外儿童和青少年糖尿病学研究进展,可以更好地了解我国儿童糖尿病研究方面与世界研究方面的差距,从而为我国以后的研究指明方向.     

人白介素18基因启动子多态性与儿童1型糖尿病的相关性研究

目的研究IL-18基因单核苷酸多态性与儿童1型糖尿病（T1DM）的关系。方法应用聚合酶链反应．序列特异性引物（PCR-SSP）和测序的方法,检测118例1型糖尿病患儿和150例正常儿童IL-18基因．137位点C／G和-607位点C／A单核苷酸的多态性。结果①IL-18基因-607位点C／A的-607A等位基因在T1DM和对照组中的发生率分别为41％和53％,差异有统计学意义（P=0．01）,两组间．137位点C／G的等位基因差异无统计学意义（P=0．37）;②IL-18基因．137位点的CC、CG和GG基因型在T1DM和对照组中差异均无统计学意义（P〉0．05）;-607位点的CC基因型T1DM组显著高于正常对照组（P=0．03）,AA基因型T1DM组显著低于正常对照组（P=0．03）;IL-18基因-607位点的CC基因型的新发糖尿病患儿更易发生酮症酸中毒。③IL-18基因的-137G／-607C单体基因型在T1DM和正常对照组间的分布频率差异有统计学意义（P=0．03）。结论IL-18基因-607位点的CC基因型和-137G／-607C单体基因型可能与儿童1型糖尿病的发病有关,而-607位点的AA基因型可能是T1DM的保护性基因型。-607位点的CC基因型与儿童1型糖尿病患者临床表型存在显著的相关性。     

Effects of prior hypoglycemia and hyperglycemia on cognition in children with type 1 diabetes mellitus

Objective:  Despite the general consensus that youth with type 1 diabetes mellitus (T1DM) can experience modest cognitive impairment, debate continues over the role of severe hypoglycemia (Hypo) and/or hyperglycemia (Hyper) in producing such impairment. Our aim was to determine how Hypo and Hyper experienced during brain development predict patterns of subsequent cognitive performance in youth with T1DM.
Methods:  We tested youth aged 5–16 yr (T1DM, n = 117; non-diabetic sibling controls, n = 58) on cognitive tasks (verbal and spatial intelligence, verbal and spatial memory, and processing speed). T1DM participants were categorized as having experienced 0, 1–2, or 3 or more (3+) Hypo episodes, as having their first Hypo episode before or after 5 yr of age and as having early (before age 5) or late (after age 5) diabetes onset. Hyper exposure was estimated with median hemoglobin A1c, adjusted for diabetes duration for each subject.
Results:  The group with T1DM had lower estimated verbal intelligence than sibling controls. Within the T1DM group, verbal intelligence was reduced with increased exposure to Hyper, not to Hypo. In contrast, spatial intelligence and delayed recall were reduced only with repeated Hypo, particularly when Hypo episodes occurred before the age of 5 yr. Age of onset did not explain these results.
Conclusions:  Hypo and Hyper have qualitatively different effects on cognitive function in T1DM that depend in part on the timing of exposure during development, independent of onset age. This information extends the known benefits of avoiding both Hypo and chronic Hyper during childhood to include preservation of specific cognitive skills.     

Echocardiographic load-independent indices of contractility in children and adolescents with type I diabetes: Effect of metabolic control and insulin on left ventricular performance

A case-control study was carried out in a tertiary referral teaching hospital to evaluate left ventricular contractility in children and adolescents with type 1 diabetes and to study factors influencing left ventricular contractility. Thirty-four children and young adults with type 1 diabetes (age 10.8–21.8 years) were randomly selected from approximately 400 patients of the same age range in the outpatient department and compared with 16 nondiabetic controls (age 7.3–21.2 years). The relation of end-systolic wall stress to velocity of circumferential fiber shortening as a standard deviation score (SDS) from the normal range described by Colan et al. was used to assess left ventricular contractility. In the diabetic group the effect of age, duration of diabetes, metabolic control, insulin dose, and autonomic function on left ventricular contractility were studied. It was found that the end-systolic wall stress-velocity of circumferential fiber shortening relation was not different between diabetic subjects and controls [+0.52 (SEM 0.21) vs +0.90 (SEM 0.26) SDS,p=0.3]. In the diabetic subjects, the end-systolic wall stress-velocity of circumferential fiber shortening relation was positively correlated with glycated hemoglobin (r=0.37,p=0.03) and insulin dose per kilogram of body weight (r=0.36,p=0.04). Those two variables together explained 24% of the variability in the end-systolic wall stress-velocity of circumferential fiber shortening relation. Twenty-eight of the diabetic subjects were also assessed for cardiac autonomic function. Disturbances of cardiac autonomic function were not associated with increased contractility. It is concluded that left ventricular contractility assessed by load-independent echocardiographic indices was not different between children and adolescents with type 1 diabetes and controls. However, increased contractility was positively related to unfavorable metabolic control and higher insulin dose.     

Reducing postprandial hyperglycemia with adjuvant premeal pramlintide and postmeal insulin in children with type 1 diabetes mellitus

Objective:  The purpose of this study was to determine the effect of adjuvant premeal pramlintide with postmeal insulin on postprandial hyperglycemia in children with type 1 diabetes mellitus (T1DM).
Methods:  Eight adolescents with T1DM on intensive insulin therapy participated in an open-label, non-randomized, crossover study, comparing postprandial glucose excursions in study A (prescribed insulin regimen and given premeal) vs. study B (pramlintide + insulin). Prandial insulin dose for study B was decreased by 20% and given postmeal, while pramlintide was given just before the meal. Blood glucose (BG), glucagon, and pramlintide concentrations were measured basally and at timed intervals during a 300-min study period.
Results:  Postprandial incremental BG for the duration of the study was reduced in study B vs. study A with AUC_{(−60 to 300 min)} (area under the curve) at 6600 ± 2371 vs. 20 230 ± 3126 mg/dL/min (367 ± 132 vs. 1124 ± 174 mmol/L/min) (p < 0.001). Glucagon concentration was suppressed for ∼120 min following administration of 30 μg of pramlintide and postmeal insulin (p < 0.003). No severe hypoglycemic episodes were experienced in this study.
Conclusions:  Postprandial hyperglycemia is considerably reduced in adolescents with T1DM when treated with fixed-dose premeal pramlintide, and precisely calculated postmeal insulin, without significant side effects.     

Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus

El‐Karaksy HM, Anwar G, Esmat G, Mansour S, Sabry M, Helmy H, El‐Hennawy A, Fouad H. Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus. Background and aim: Children with type 1 diabetes mellitus (T1DM) are frequently investigated for hepatic abnormalities. This study was carried out to report on the prevalence of hepatic abnormalities in diabetic children and adolescents and to highlight the possible etiology and appropriate management. Methods: The study included 692 children (333 were males) with T1DM attending the Diabetes Unit at Cairo University Pediatric Hospital. Their mean age was 9.65 ± 4.18 yr. All children were subjected to clinical examination for hepatomegaly, determination of alanine aminotransferase (ALT) and antibodies to hepatitis C virus (anti‐HCV), and abdominal ultrasonography. All children with clinical, laboratory or ultrasound abnormality were counseled about proper glycemic control and followed up. If abnormalities persisted, more detailed investigations were carried out. HCV RNA was done for anti‐HCV positive children. Results: Sixty (8.7%) were found to have one or more abnormalities: clinical hepatomegaly in 13 (1.9%), elevated ALT in 27 (3.9%), anti‐HCV in 25 (3.6%) and abnormal hepatic ultrasound in 31 (4.5%). Forty percent of anti‐HCV positive children were HCV‐RNA positive. Glycogenic hepatopathy was diagnosed in three cases by liver biopsy. Abnormalities were reversible in 37/60 after proper glycemic control. Conclusion: Although diabetic children are at risk of acquisition of HCV, poor glycemic control is the key factor that predisposes to hepatomegaly, elevated ALT and abnormal ultrasound findings. A 4 to 8‐wk therapeutic trial of proper glycemic control is recommended prior to more invasive diagnostic procedures.     

Autonomic blood pressure control in children and adolescents with type 1 diabetes mellitus

Introduction:  Increased daytime blood pressure and reduced nocturnal dipping can already be found in children with type 1 diabetes mellitus. We hypothesized that impaired baroreflex sensitivity can cause this abnormal blood pressure behavior in children and adolescents with type 1 diabetes, reflecting an early stage of diabetic autonomic neuropathy.
Methods:  In the present study, we monitored beat-to-beat blood pressure and pulse interval non-invasively with portapres© in 38 patients with type 1 diabetes (7–18 yr) and 14 non-diabetic subjects (5–17 yr). The Trigonometric Regressive Spectral Analysis was used to assign spontaneous oscillations of blood pressure and pulse interval to defined frequency bands between 0.003 and 1.0 Hz and to calculate baroreflex sensitivity. Correlations with diabetes-specific data like hemoglobin A1c (HbA1c) and with 24-h blood pressure measurements were calculated.
Results:  The diabetic subjects displayed significantly less variance of blood pressure and pulse interval in the high frequency (HF) bands and a lower BRS. BRS decreased with higher HbA1c and daily insulin dose. We also saw significant changes in spectral variance of blood pressure and pulse interval with these parameters. Patients with higher sympathetic activity (LF/HF-ratio) during daytime measurements displayed more nocturnal dipping.
Conclusion:  Our data evidence impaired baroreflex sensitivity in children and adolescents with type 1 diabetes mellitus. We suggest spectral analysis of spontaneous blood pressure and pulse interval oscillations during night sleep to further pursue the role of baroreflex sensitivity in the etiology of the non-dipping phenomenon in diabetic patients.     

Prevalence of type 1 diabetes mellitus in 6-18-yr-old school children living in Istanbul, Turkey

Akesen E, Turan S, Güran T, Atay Z, Save D, Bereket A. Prevalence of type 1 diabetes mellitus in 6–18‐yr‐old school children living in Istanbul, Turkey. Background: Type 1 diabetes mellitus (T1DM) is among the most common chronic diseases in childhood and the incidence of T1DM is increasing worldwide. There is no actual data regarding the frequency of T1DM in Turkish children. Objectives: We aimed to assess current prevalence of T1DM in 6–18‐yr‐old school children living in Istanbul. Methods: Total number of students and children on insulin treatment were reported by the schools, as the first part of the study. At the second step, the study team visited 203 schools for confirmation of the reported data. Results: One thousand and ninety children in a population of 1 630 751 school children were reported to have T1DM, which made the total prevalence of T1DM 0.67/1000 (95% confidence interval 0.6/1000–0.7/1000). A population of 217 030 children (α = 0.05 and β = 0.20) from 203 schools were screened. The difference between the reported and detected prevalence was 0.032/1000 (215 detected vs. 222 reported, p > 0.05). Comparison of the current data with the prevalence reported in a smaller population in Ankara, Turkey, 16 yr ago, demonstrated that the prevalence of T1DM is higher in the current study (0.46/1000 vs. 0.16/1000, 0.57/1000 vs. 0.34/1000, and 0.92/1000 vs. 0.69/1000 at primary, secondary, and high schools, respectively). Conclusion: This first pediatric T1DM prevalence data in a large pediatric population in Istanbul, Turkey, estimated the prevalence of T1DM as 0.67/1000. This prevalence is 2.5‐fold higher than that reported in Ankara, Turkey, in 1993, suggesting that T1DM prevalence is increasing in Turkey as in the other parts of the world.