Type 2 diabetes mellitus in children and adolescents: a review from a European perspective

Changes in food consumption and exercise are fueling a worldwide increase in obesity in children and adolescents. As a consequence of this dramatic development, an increasing rate of type 2 diabetes mellitus has been recorded in children and adolescents in the USA and, more recently, in many countries around the world. Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes. Lower susceptibility in white Caucasians and higher susceptibility in Asians, Hispanics and blacks have been noted. There is a high hidden prevalence and a lack of exact data on the epidemiology of the disease in Europe: in Germany only 70 patients below the age of 15 years were identified in the systematic, nationwide DPV (Diabetessoftware für prospektive Verlaufsdokumentation) diabetes survey, but our calculations suggest that more than 5000 young people in Germany at present would meet the diagnostic criteria of type 2 diabetes. In Australasia, the prevalence of type 2 diabetes is reportedly high in some ethnic groups and again is linked very closely to the obesity epidemic. No uniform and evidence-based treatment strategy is available: many groups use metformin, exercise programmes and nutritional education as a comprehensive approach to treat type 2 diabetes in childhood and adolescence. The lack of clear epidemiological data and a strong need for accepted treatment strategies point to the key role of preventive programmes. Prevention of obesity will help to counteract the emerging worldwide epidemic of type 2 diabetes in youth. Preventive programmes should focus on exercise training and reducing sedentary behaviour such as television viewing, encouraging healthy nutrition and supporting general education programmes since shorter school education is clearly associated with higher rates of obesity and hence the susceptibility of an individual to acquire type 2 diabetes.     

Presentation and 5-year follow-up of type 2 diabetes mellitus in African-American and Caribbean-Hispanic adolescents

OBJECTIVE: We report the presentation and 5-year follow-up of 89 African-American (AA) and Caribbean-Hispanic (CH) youths with type 2 diabetes mellitus (T2DM) followed at the Montefiore Medical Center, Bronx, N.Y., USA, from 1990 to 2000. METHODS: The medical records of 89 patients with T2DM diagnosed between 1990 and 2000 were reviewed. RESULTS: Over a 10-year period, the number of pediatric patients less than 18 years of age diagnosed with T2DM at the Montefiore Medical Center increased tenfold. At presentation, the mean age was 14 +/- 2.3 years, the mean body mass index (BMI) was 34.4 +/- 9 kg/m(2), the female/male ratio was 1.6:1, and all these patients were pubertal. Acanthosis nigricans was present in 89% of the patients, polyuria and polydipsia occurred in 48%, weight loss occurred in 22%, and nearly 30% of the patients were asymptomatic at diagnosis. Diabetic ketoacidosis occurred in 5 patients. By 5 years after diagnosis, 45% of the patients were able to maintain an HgbA1C <7% with oral medications (metformin and/or glipizide); 18% required insulin (<0.4 U/kg/day) in addition to oral medications, and 37% did not require any medication. The mean insulin level, BMI and HgbA1C at the time of diagnosis did not predict treatment requirements for 3 years after diagnosis. CONCLUSIONS: Because the incidence of T2DM is increasing in adolescents, the natural history and optimal therapy for adolescents with T2DM need to be established.     

Metabolomics based markers predict type 2 diabetes in a 14-year follow-up study

Background

The growing field of metabolomics has opened up new opportunities for prediction of type 2 diabetes (T2D) going beyond the classical biochemistry assays.

Objectives

We aimed to identify markers from different pathways which represent early metabolic changes and test their predictive performance for T2D, as compared to the performance of traditional risk factors (TRF).

Methods

We analyzed 2776 participants from the Erasmus Rucphen Family study from which 1571 disease free individuals were followed up to 14-years. The targeted metabolomics measurements at baseline were performed by three different platforms using either nuclear magnetic resonance spectroscopy or mass spectrometry. We selected 24 T2D markers by using Least Absolute Shrinkage and Selection operator (LASSO) regression and tested their association to incidence of disease during follow-up.

Results

The 24 markers i.e. high-density, low-density and very low-density lipoprotein sub-fractions, certain triglycerides, amino acids, and small intermediate compounds predicted future T2D with an area under the curve (AUC) of 0.81. The performance of the metabolic markers compared to glucose was significantly higher among the young (age?<?50 years) (0.86 vs. 0.77, p-value <0.0001), the female (0.88 vs. 0.84, p-value =0.009), and the lean (BMI?<?25 kg/m²) (0.85 vs. 0.80, p-value =0.003). The full model with fasting glucose, TRFs, and metabolic markers yielded the best prediction model (AUC?=?0.89).

Conclusions

Our novel prediction model increases the long-term prediction performance in combination with classical measurements, brings a higher resolution over the complexity of the lipoprotein component, increasing the specificity for individuals in the low risk group.

     

Type 2 diabetes in children: clinical aspects and risk factors

In the past, type 2 diabetes mellitus was considered a disease of adults and older individuals, not a paediatric condition. Over the last decade, however, in the USA and the rest of the world there has been a disturbing trend of increasing cases of type 2 diabetes in children, mirroring increasing rates of obesity. The risk factors for paediatric type 2 diabetes are: (1) obesity and increased body mass index; (2) family history of type 2 diabetes; (3) membership of ethnic minority; (4) puberty (mean age of diagnosis is approximately 13.5 years); (5) female gender; and (6) features of 'syndrome X'. The common link among these risk factors is insulin resistance, which plays a pivotal role in the pathophysiology of type 2 diabetes. Both insulin resistance and beta-cell failure are present in the fully established diabetes state. Data will be presented on how these risk factors impact on insulin sensitivity and insulin secretion in childhood, ultimately leading to type 2 diabetes. The clinical presentation of type 2 diabetes in children and its distinction from type 1 diabetes will be discussed.     

Development of impaired glucose tolerance and diabetes in follow-up offspring of Caribbean patients with type 2 diabetes: analysis of 5-year follow-up study

Several reports agreed that the antecedent markers for developing diabetes in offspring of type 2 diabetic patients involve excess body weight and insulin resistance. This study examined the pattern of changes in anthropometric and biochemical risk factors for developing diabetes in a follow-up offspring of Caribbean type 2 diabetic patients. Results of 46 offspring of type 2 diabetic patients who had received one-to-one individualized diet and exercise counseling for 5 years in our laboratory were analyzed. Changes in anthropometric (body weight, waist circumference) and biochemical (insulin, glucose, lipids, HOMA-insulin resistance, HOMA-percent beta-cell function) parameters over the 5-year period were analyzed using ANOVA tests. Of the 46 offspring, 10.9 and 2.2%, respectively, developed impaired glucose tolerance (IGT) and diabetes. Over the years, IGT offspring had a significant step-wise increase and decrease in fasting and 2-h postprandial plasma glucose levels (P < 0.05) and percent B-cell function (P < 0.001), respectively. Again, a non-significant step-wise increase was observed in body mass index, waist circumference and HOMA-insulin resistance levels (P > 0.05). While we await the results of medication-based intervention studies in different populations, exercise and diet counseling will remain the only available lifestyle intervention strategy for slowing IGT progression to diabetes.     

A therapeutic alternative for tension headache in children: Treatment and 1-year follow-up results

Ten young subjects, ranging in age from 12 to 15 years, suffering from tension headache were treated by electromyographic biofeedback (EMG-BFB) twice a week for 12 sessions. The Pain Total Index (PTI) was recorded every month from the beginning to the end of the treatment. At the end of the treatment the PTI decreased significantly in all our patients and, at the same time, the muscular tension values also decreased. This result supports the hypothesis of a correlation between clinical symptom and muscular tension level. We saw our patients for follow-up sessions, and the clinical improvement was confirmed to 1 year from the completion of the treatment; however, the muscular tension values were increased with respect to the last-session values.     

Free-flap mandibular reconstruction: a 10-year follow-up study

Free-flap reconstruction of oncologic mandibular defects has become the modern standard of care. However, no previous studies have established the long-term results of such reconstructions. The objective of this study was to review functional and aesthetic outcomes in patients a decade after free-flap mandibular reconstruction.A single surgeon's experience with free-flap reconstruction of the mandible was retrospectively reviewed. Eighty-two consecutive patients who underwent reconstruction from January of 1987 to December of 1990 were identified. Of the 34 patients still alive, 20 agreed to participate (response rate, 59 percent). To assess complications and functional outcome, patients were interviewed using validated questions and questions developed specifically for the study. Aesthetic outcome was judged by two independent observers. Panorex radiographs were obtained to assess bone resorption. Bone height was measured at standardized locations on the body, ramus, and symphysis and compared with the immediate postoperative Panorex radiographs. Differences in Panorex magnification were adjusted for by comparison of miniplate measurements. Mean length of follow-up was 11 years. Mean patient age at the time of the study was 48 years. Nineteen of 20 patients had malignant disease, one of whom had a local recurrence during the follow-up period. Two patients received radiation therapy preoperatively and 13 postoperatively. Mean length of mandible resection was 13 cm. Defect types were as follows (Jewer's classification): 12 L, 4 H, 3 LC, and 1 LCL. All flaps survived.At 10-year follow-up, aesthetic outcome was judged to be excellent in 55 percent of patients, good in 20 percent, fair in 15 percent, and poor in 10 percent. The aesthetic results were remarkably stable over time. Slight accentuation of subtle postoperative asymmetry became evident as facial aging progressed. Dental rehabilitation in the study group included five patients with osteointegrated implants and seven with conventional dentures. Seventy percent of patients reported a regular diet. The remainder required a soft diet. Food tolerance was good, as rated by the List Scale (mean score, 77 percent). Seventeen patients had easily intelligible speech, whereas three were intelligible with effort. At the midbody of the mandible, 92 percent of the postoperative bone height was preserved; at the midramus, 93 percent was maintained; and at the symphysis, 92 percent remained. In several patients, there was greater age-related bone loss from the residual native mandible compared with the reconstructed site. One patient developed an orocutaneous fistula following postoperative radiation therapy. Nine patients had miniplates removed, either because of plate problems or to allow implant placement. There were no cases of osteoradionecrosis, bone fracture, or miniplate fracture. There was no significant long-term disability related to the donor site.Free-flap reconstruction of the mandible provides excellent functional and aesthetic results that remain stable over time. Bone resorption is surprisingly minimal, even in the face of postoperative radiation therapy. The majority of patients are able to tolerate a regular diet and to either wear dentures or acquire osteointegrated implants. Acceptable speech and appearance are restored and continue to be a source of patient satisfaction at least a decade after surgery.     

Cross-cultural differences in the management of children and adolescents with diabetes

Glycaemic control deteriorates frequently in adolescents with diabetes. There is a considerable body of work on the effect of psychological aspects of management in this age group, but few randomized controlled trials of the effect of specific behavioural therapy and lifestyle modification on the improvement of glycaemic control. Of recent interest have been the observations from the Hvid?re Study Group on cross-cultural differences in glycaemic control. The average glycosylated haemoglobin in 22 centres, across 18 countries, varied in young people, with HbA1c levels ranging from 7.6 to 10.2%. No obvious differences in management were identified in this survey that could account for the disparities in glycaemic control. Data from the Scottish Study Group demonstrated similar variation in average glycaemic control in centres across a single culture. Using the qualitative methodology of anthropological research, some specific factors were identified that appear to influence young people's response to diabetes management and strategies employed by health professionals in their advice and care of the diabetes, particularly in relation to intensive insulin regimens. The main cultural factors influencing glycaemic control appear to be communication, reciprocal support between young people and professional heart carers and family structure within an individualistic, as against an egalitarian, society. Shared beliefs about teenage risk behaviour together with the medicalization of adolescence within medical culture also appears to be highly influential. The aim of this educational discussion group was to explore how a variety of health care professionals from distinctive cultures approach diabetes care delivery in this age group. The specific success and difficulties in different cultures in managing the young person with diabetes were investigated. Also discussed was how qualitative research methodology may generate further research in this area.     

Presence and gradual disappearance of filaria-specific urinary IgG4 in babies born to antibody-positive mothers: a 2-year follow-up study

A total of 14 Sri Lankan pregnant women, who were anti-Brugia pahangi urinary IgG4 positive, and their 14 newborn babies were followed up for the urinary antibody for 2 years by enzyme-linked immunosorbent assay. Eight babies showed positive IgG4 reaction, at least once within 4 months after birth. Urinary antibody titers of mothers and their babies measured around the perinatal period showed a significant positive correlation, suggesting that baby's IgG4 was transferred from the mother through the placenta. The IgG4 decreased gradually and became negative in all positive babies by day 339.3 after birth. The present result provides a basis to judge if a positive urine ELISA test among babies is due to a new filarial infection.     

Type 2 diabetes as a lipid disorder

Diabetic dyslipidemia is a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. The recognition that the elevation of large VLDL 1 particles initiates a sequence of events that leads to the formation of small dense LDL and HDL species has focused the assembly of VLDL particles on the spotlight as a potential culprit of dyslipidemia. Notably dyslipidemia is associated with insulin resistance, visceral obesity and liver fat content. Insulin resistance is associated with excessive flux of substrates for VLDL assembly to the liver as well as the upregulation of the machinery generating large VLDL particles in excess. The regulation of different molecular steps in this cascade of events are complex and so far poorly understood. The disordered crosstalk between adipose tissue and the liver results in an imbalance of the machinery that orchestrates the regulation of VLDL production. A number of studies indicates that adipocytokines in particular adiponectin may be a seminal player in the regulation of fat metabolism in the liver. Future discoveries hopefully will delineate the regulatory steps to allow more targeted treatment of diabetic dyslipidemia.     

Medication adherence in type 2 diabetes: the ENTRED study 2007, a French Population-Based Study

Background

Adherence to prescribed medications is a key dimension of healthcare quality. The aim of this large population-based study was to evaluate self-reported medication adherence and to identify factors linked with poor adherence in patients with type 2 diabetes in France.

Methodology

The ENTRED study 2007, a French national survey of people treated for diabetes, was based on a representative sample of patients who claimed reimbursement for oral hypoglycaemic agents and/or insulin at least three times between August 2006 and July 2007, and who were randomly selected from the database of the two main National Health Insurance Systems. Medication adherence was determined using a six-item self-administered questionnaire. A multinomial polychotomous logistic regression model was used to identify factors associated with medication adherence in the 3,637 persons with type 2 diabetes.

Principal Findings

Thirty nine percent of patients reported good medication adherence, 49% medium adherence and 12% poor adherence. The factors significantly associated with poor adherence in multivariate analysis were socio-demographic factors: age <45 years, non-European geographical origin, financial difficulties and being professionally active; disease and therapy-related factors: HbA_1c>8% and existing diabetes complications; and health care-related factors: difficulties for taking medication alone, decision making by the patient only, poor acceptability of medical recommendations, lack of family or social support, need for information on treatment, reporting no confidence in the future, need for medical support and follow-up by a specialist physician.

Conclusions

In a country with a high level of access to healthcare, our study demonstrated a substantial low level of medication adherence in type 2 diabetic patients. Better identification of those with poor adherence and individualised suitable recommendations remain essential for better healthcare management.