Peripheral sensory nerve dysfunction in children and adolescents with Type 1 diabetes mellitus

The aim of the present study was to investigate peripheral sensory nerve function in diabetic children and adolescents without neurological symptoms. Ninety-two children and adolescents with Type 1 (insulin-dependent) diabetes mellitus (mean ± SD age: 14.2 ± 2.1 years, diabetes duration: 5.8 ± 3.0 years) and 80 healthy control subjects (age: 13.8 ± 2.2 years) matched for age, sex, body mass index, and height standard deviation score were involved in the study. Using a sine-wave transcutaneous stimulator, current perception threshold (CPT) testing at 2000, 250 and 5 Hz was performed on the left median and peroneal nerves. Diabetic children had increased CPT at 2000 Hz on both nerves as compared to the control group (median (interquartile range), median nerve: 2.43 (2.20–3.43) vs 1.80 (1.51–2.60) mA, p = 0.02; peroneal nerve: 3.51 (2.81–4.82) vs 2.70 (2.04–3.70) mA, p = 0.01). Twenty-one (23 %) of patients had CPT values higher than that of any healthy individual. Of these, elevated CPT was observed in 9 (9.8 %) patients on the median nerve, in 8 (8.7 %) patients on the peroneal nerve, and in 4 (4.3 %) patients on both median and peroneal nerves. Using multiple logistic regression analysis, worse long-term metabolic control and advanced puberty were independently predictive of peripheral sensory nerve dysfunction as the dependent variable (adjusted OR (95 % CI): 3.4 (1.2–6.2), p = 0.01, and 2.8 (1.1–5.6), p = 0.03, respectively). In conclusion, evidence of peripheral sensory nerve dysfunction is not rare in children and adolescents with diabetes and can be demonstrated by CPT testing in asymptomatic patients. Poor metabolic control is a risk factor for such subclinical neuropathy, and pubertal development may be involved in the pathogenesis of diabetic peripheral neuropathy. © 1998 John Wiley & Sons, Ltd.     

Type 2 diabetes and the metabolic syndrome in children and adolescents

The prevalence rates of obesity, metabolic syndrome, and type 2 diabetes in children are increasing at an alarming rate. The potential impact of these conditions on the individual, the family, and society, especially in regard to the costs and utilization of health care resources, are very serious. Strategies aimed at reducing caloric intake, increasing caloric expenditure through regular exercise, and treating cardiovascular risk factors and type 2 diabetes early and aggressively are necessary to meet the challenges they impose.     

Acute and chronic complications of type 2 diabetes mellitus in children and adolescents

With the increase in prevalence of type 2 diabetes mellitus in adolescents, a rise in incidence of secondary comorbidities--including hypertension, hyperlipidaemia, nephropathy, and retinopathy--is anticipated. Furthermore, findings of studies in young adults have suggested that the development and progression of clinical complications might be especially rapid when the onset of type 2 diabetes is early, raising the possibility of a serious public-health challenge in the next few decades. To date, reports of the epidemiology and natural history of secondary complications specifically in adolescents with type 2 diabetes have been scarce. Yet, we must begin to understand the extent of the coming challenge. To this end, we have reviewed reports on acute and long-term comorbidities associated with type 2 diabetes in young people and have looked at mounting evidence that this group could be at increased risk for development of early complications.     

Subclinical pain and thermal sensory dysfunction in children and adolescents with Type 1 diabetes mellitus.

AIMS: To assess cutaneous thermal and pain thresholds in upper and lower limbs in neurologically asymptomatic children and adolescents, and to study the relationships of clinical parameters and these sensory thresholds in subclinical diabetic neuropathy. METHODS: Thirty-five neurologically asymptomatic patients, aged 8-16 years, diagnosed with Type 1 diabetes mellitus (DM), and a control group of 35 healthy age-matched subjects participated in the study. Warmth, cold, and heat-induced pain thresholds were measured in the dorsum of the right arm and foot, using quantitative sensory testing (QST). Relevant clinical parameters, retrieved from medical records or measured at the QST session, were obtained for each patient. RESULTS: Compared with controls, diabetic patients had increased thresholds for warmth in the hand (P = 0.002), and cold and warmth in the foot (P = 0.015 and P = 0.004, respectively). Of the diabetic patients, 43% showed abnormality of at least one sensory threshold. A significant correlation was observed for duration of diabetes and heat-induced pain threshold in the hand (P = 0.045), but no correlation was found for age, height, weight, pre-test blood glucose, age of onset, current insulin dose, and mean of glycosylated haemoglobin determinations of the previous 18 months. No significant correlation was found for other sensory thresholds. CONCLUSIONS: Using QST, abnormal cutaneous thermal perception is a common finding, in both upper and lower limbs, in neurologically asymptomatic young diabetic patients. Heat-induced pain threshold in the hand was correlated with the duration of the diabetes.     

Type 2 diabetes mellitus and bone

Type 2 diabetes (T2DM) is a rapidly growing public health problem. It is associated with an increased risk of fracture, particularly of the hip, despite normal or high bone mineral density. Longer duration of disease and poor glycaemic control are both associated with higher fracture risk. The factors underlying increased fracture risk have not been clearly established, but increased falls risk, obesity, sarcopenia and co‐morbidities are likely to contribute. The basis for reduced bone strength despite higher bone mineral density remains to be fully elucidated. Bone turnover is reduced in individuals with T2DM, with evidence of impaired bone formation. Most studies indicate normal or superior trabecular bone structure although reduced lumbar spine trabecular bone score (TBS) has been reported. Deficits in cortical bone structure have been demonstrated in some, but not all, studies whilst reduced bone material strength index (BMSi), as assessed by microindentation, has been a consistent finding. Accumulation of advanced glycation end products in bone may also contribute to reduced bone strength. The use of FRAX in individuals with T2DM underestimates fracture probability. Clinical management should focus on falls prevention strategies, avoidance of known risk factors, maintenance of good glycaemic control and bone protective intervention in individuals at high risk of fracture. Dietary and surgical strategies to reduce weight have beneficial effects on diabetes but may have adverse effects on skeletal health. Future research priorities include better definition of the mechanisms underlying increased fracture risk in T2DM and optimal strategies for identifying and treating those at high risk.     

Cerebral vasoreactivity in children and adolescents with type 1 diabetes mellitus

It is well established in clinical and experimental settings that diabetes mellitus, especially if long lasting, impairs autoregulation of cerebral blood flow (CBF). However, the onset and the course of development of this dysfunction remain unknown. We hypothesized that assessment of autoregulatory functions of cerebral arteries in children with relatively short duration of type 1 diabetes mellitus may provide an insight into the pathophysiology of the development of impaired autoregulation of CBF. Such a dysfunction of vasodilation of cerebral arteries can be assessed by transcranial Doppler. Therefore, to examine whether and when autoregulation of CBF becomes affected by diabetes, we used transcranial Doppler and a pCO2 challenge in 17 males between the ages of 12-20 years with type 1 diabetes mellitus of 0.2-16 years duration and with varying degrees of glucose control. The results were compared with age-matched, healthy, nondiabetic controls. The CO2 challenge increased cerebral blood-flow velocities and decreased the pulsatility index. These changes were not influenced by the presence or duration of diabetes, insulin dose, or degree of diabetic control.     

Tobacco smoke exposure in children and adolescents with diabetes mellitus.

AIMS: To examine active and passive tobacco smoke exposure in children and adolescents attending a diabetic clinic. METHODS: Salivary cotinine concentrations were measured by gas chromatography and questionnaire data on the smoking habits of patients, families and friends were analysed as well as recording of glycosylated haemoglobin (HbA1c), body mass index (BMI) and social deprivation score. RESULTS: Salivary cotinine concentrations identified 7% of the patients as active smokers and 72% as passive smokers. The mean cotinine concentration in those with no identifiable source of exposure was 0.10 (95% confidence interval 0.05-0.14) ng/ml, 2.81 (2.24-3.38) ng/ml in the passive smoking group and 1003.69 (55.96-151.41) ng/ml in the active smokers. Cotinine concentrations in passive smokers increased with the number of sources of exposure. The mean cotinine concentration was also higher when the mother was the sole source compared to other sources. There was no statistically significant correlation to smoking exposure and HbA1c BMI and deprivation scores. CONCLUSION: Tobacco smoke exposure may pose serious health risks to children and adolescents with diabetes and additional public health measures are required to reduce overall exposure.     

Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus

Aims/hypothesis

Deterioration of microvascular function may have an early onset in individuals with type 1 diabetes mellitus. We hypothesised that microvascular autoregulation is impaired in children with type 1 diabetes and can be detected non-invasively by postocclusive reactive hyperaemia (PORH).

Methods

Microvascular autoregulation was assessed in 58 children with type 1 diabetes and 58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry. Baseline perfusion, biological zero (defined as a ‘no flow’ laser Doppler signal during suprasystolic occlusion), peak perfusion following occlusion, time to peak and recovery time (time until baseline perfusion is resumed) were recorded and compared between the groups.

Results

Peak perfusion was higher in children with type 1 diabetes than in healthy controls (1.7?±?0.93?AU [arbitrary units] vs 1.29?±?0.46?AU; p?=?0.004), and biological zero was lower in children with type 1 diabetes vs controls (0.14?±?0.04?AU vs 0.19?±?0.04?AU; p?Conclusions/interpretation PORH reveals impaired microvascular autoregulation in children with type 1 diabetes. The higher peak perfusion might reflect a decline in the vasoconstrictive ability of arteriolar smooth muscle cells upstream of capillary beds in children with type 1 diabetes.     

Glycosuria and diabetes mellitus in children and adolescents in south India.

In Madras city (India) 10,513 school students between 3 and 20 yr of age were investigated for glycosuria and its causes. While no previously known cases of diabetes mellitus of any type were encountered, four students (0.038%) in the survey population were found to have glycosuria. One (0.009%) had renal glycosuria, two (0.019%) were possibly NIDDY (MODY) and one (0.009%) had transient glycosuria while receiving anti-tuberculous chemotherapy. It is therefore concluded that neither diabetes mellitus nor glycosuria of non-diabetic causes is a crucial health problem in Indian children and adolescents. While the reasons for this are not known, further research in this field could be of global interest.     

Type II diabetes mellitus and impaired glucose regulation in Caucasian children and adolescents with obesity living in Germany

BACKGROUND: Recent studies reported an increased prevalence of type II diabetes mellitus in obese children and adolescents, especially in specific ethnic subgroups. The aim of this study was to determine the prevalence of type II diabetes mellitus and impaired glucose regulation in a large group of Caucasian children and adolescents with obesity living in Germany. PATIENTS AND METHODS: A total of 520 subjects (237 boys, 283 girls) (mean age: 14.0+/-2.0 y (range 8.9-20.4 y)) with a BMI>97th percentile, BMI-SDS: 2.7+/-0.5 (range 1.9-4.6), who were consecutively admitted to an in-patient obesity unit participated in the study. A 2-h oral glucose tolerance test (1.75 mg of glucose per kilogram of body weight) was performed before entering a weight-loss program and capillary blood glucose concentrations were measured. Patients were categorized into normal glucose regulation, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. In addition, fasting venous blood was taken to determine the circulating insulin, C-peptide and lipids. Insulin resistance was estimated by homeostatic model assessment. RESULTS: Type II diabetes was present in 1.5% (n=8) of the patients, two patients were admitted with already diagnosed type II diabetes and six patients were identified with yet unknown diabetes. IFG was detected in 3.7% (n=19) and IGT in 2.1% (n=11) of the patients. All together, in 6.7% (n=35) (95% confidence interval: 4.7-9.2%) of the patients, impaired glucose regulation (IFG, IGT) or diabetes was identified. These patients had a higher BMI-SDS, higher levels of fasting insulin and C-peptide and a higher insulin resistance index than the patients with normal glucose regulation. Risk factors for the occurrence of impaired glucose regulation were a BMI-SDS>2.5 as well as a positive parents' history for diabetes. CONCLUSIONS: This is the first report on the prevalence of type II diabetes in a large cohort of Caucasian children and adolescents with obesity living in Europe. Impaired glucose regulation and type II diabetes were present in a substantial proportion of the patients studied. Screening for diabetes in severely obese children and adolescents (BMI-SDS>2.5) is therefore recommended. Patients identified with impaired glucose regulation need specific treatment programs in order to prevent progression to diabetes.     

Type 2 diabetes mellitus is becoming the most common type of diabetes in school children

Abstract. Obesity, now an epidemic in the USA, northern Europe, and Italy, is associated with several co-morbidities that shorten life expectancy, in particular type 2 diabetes mellitus (T2DM), arterial hypertension, and hyperlipidemia. The impact of obesity on mortality is evident in all ages, and is especially strong in young persons. Obesity, especially visceral obesity, associated with a sedentary lifestyle, is among the strongest risk factors for T2DM, and a diagnosis of T2DM seems to increase linearly as a function of duration of obesity. The pathogenesis of T2DM is based on a dual defect, i. e. increased insulin resistance coupled with defective insulin release. The main abnormality in obesity is increased insulin resistance, while insulin release, even though defective compared with body needs, is usually abundant.The incidence of obesity among children aged 6-16 years is now even greater than that among adults: in Italy, figures up to 30% have been reported. As in adults, obesity is a cause, among children, of arterial hypertension, left ventricular hypertrophy, hyperlipidemia, non-alcoholic-steato hepatitis, sleep apnea syndrome (SAS), and orthopedic, psychological, and social problems. Together with an increase in body weight, there is an increase of visceral fat. Obesity in children has also led to a tremendous increase in the prevalence of impaired glucose tolerance (IGT); the percentages span from 25% in a multiethnic cohort in the USA, to 4% in Italian Caucasians. Management of obesity and of T2DM in children has to face the issue of poor compliance; there is consensus that dietary treatment of obese T2DM children is a failure, so that drugs are required; the only drug evaluated in a formal trial is metformin, that behaves in terms of efficacy and of minor side effects as in adults. In conclusion, obesity in children is not pure obesity, but is accompanied by co-morbidities that cluster to form the metabolic syndrome just like in the adults. If this epidemics continues and is not properly challenged, in the next decades we will face an epidemic of early cardiovascular morbidity and mortality.     

Type 2 diabetes in children

The emerging epidemic of type 2 diabetes (T2DM) in young people reflects increasing rates of obesity and parallels the increasing frequency of T2DM in adults. As in adults, T2DM in children is part of the insulin resistance syndrome that includes hyperandrogenism seen as premature adrenarche and polycystic ovary syndrome, hypertension, dyslipidemia, and other atherosclerosis risk factors. Recent studies in children document risk factors for T2DM, and associated cardiovascular risk factors, including obesity, family history, diabetic gestation, and underweight or overweight for gestational age. Genetically determined insulin resistance or limited β-cell reserve has been demonstrated in high-risk individuals, including first-degree relatives of girls with premature adrenarche. This genetic background, considered advantageous in a feast-and-famine existence (the thrifty genotype), is rendered detrimental with abundant food and physical inactivity, a lifestyle demonstrated to be typical of families of children with T2DM. The increasing incidence of T2DM in children and adolescents threatens to become a major public health problem. Risk factors for cardiovascular disease, hypertension, hyperlipidemia, and microalbuminuria are present at diagnosis of T2DM in Native American adolescents, indicating that insulin resistance has been present for some time before the diagnosis of diabetes was made. Case finding is likely to be beneficial in high-risk youths. Treatment is the same as that of adults. The only data on use of oral hypoglycemic agents in children have been with metformin. Community and governmental efforts to educate all children and their parents about the need for physical activity and dietary modification are essential to control this epidemic.