The management of type 2 diabetes mellitus in children and adolescents

The medical community faces an emerging epidemic of type 2 diabetes mellitus (DM2) in children and adolescents with a disproportionate increase among certain ethnic groups. DM2 represents one arm of the metabolic syndrome and parallels an increasing prevalence of obesity. The metabolic syndrome includes insulin resistance, hyperlipidemia, and hypertension with a consequent risk of early cardiovascular disease. Thus, treatment of DM2 and the metabolic syndrome poses a challenge for pediatric endocrinologists and represents a huge public health issue. This review presents information about treatment of childhood DM2 with emphasis on indications for the use of insulin in management and normalization of blood glucose.     

Overweight,obesity and features of metabolic syndrome in children with diabetes treated with insulin pump therapy

There has been no specific evaluation of atherogenic risk factors in children with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). We, therefore, studied the prevalence of overweight/obesity and metabolic syndrome among these patients. Five hundred children with T1DM treated with CSII and multiple daily insulin (MDI) regimen were included in the study. Anthropometric data/physical examination, data concerning diabetes, and a lipid profile were assessed in this group, and compared with respect to treatment method (CSII vs. MDI). Almost one-third (30.2%) of the children were overweight/obese. The body mass index (BMI) values at the time of the present evaluation were significantly higher in comparison with the BMI values 3–6 months after the diagnosis. Dyslipidemia was recognized in 51.6%, hypertension in 4.8%, and the metabolic syndrome in 3.2%. of the subjects. The overweight/obese children differed from their normal-weight counterparts with respect to metabolic control, the incidence of hypertension, dyslipidemia, and metabolic syndrome. The girls showed higher prevalence of overweight/obesity and higher BMI values compared to the boys. The children treated with CSII had the same prevalence of overweight/obesity, but a lower incidence of dyslipidemia, and a better metabolic control compared to the children treated with MDI regimen. Our study shows a high prevalence of overweight/obesity and dyslipidemia in children with T1DM including those treated with an insulin pump.     

Childhood Obesity and the Metabolic Syndrome in Developing Countries

Rapidly changing dietary practices accompanied by an increasingly sedentary lifestyle predispose to nutrition-related non-communicable diseases, including childhood obesity. Over the last 5 y, reports from several developing countries indicate prevalence rates of obesity (inclusive of overweight) >15 % in children and adolescents aged 5–19 y; Mexico 41.8 %, Brazil 22.1 %, India 22.0 % and Argentina 19.3 %. Moreover, secular trends also indicate an alarming increase in obesity in developing countries; in Brazil from 4.1 % to 13.9 % between 1974 and 1997; in China from 6.4 % to 7.7 % between 1991 and 1997; and in India from 4.9 % to 6.6 % between 2003-04 to 2005–06. Other contributory factors to childhood obesity include: high socio-economic status, residence in metropolitan cities and female gender. Childhood obesity tracks into adulthood, thus increasing the risk for conditions like the metabolic syndrome, type 2 diabetes mellitus (T2DM), polycystic ovarian syndrome, hypertension, dyslipidemia and coronary artery disease later in life. Interestingly, prevalence of the metabolic syndrome was 35.2 % among overweight Chinese adolescents. Presence of central obesity (high waist-to-hip circumference ratio) along with hypertriglyceridemia and family history of T2DM increase the odds of T2DM by 112.1 in young Asian Indians (< 40 y). Therapeutic lifestyle changes and maintenance of regular physical activity are most important strategies for preventing childhood obesity. Effective health awareness educational programs for children should be immediately initiated in developing countries, following the successful model program in India (project ‘MARG’).     

Barriers to the treatment of adolescent type 2 diabetes--a survey of provider perceptions

Objective: Type 2 diabetes mellitus (T2DM) is increasingly common among children and adolescents. However, achievement of good metabolic control has been difficult in this population. The aim of this study was to survey pediatric endocrine and diabetes specialists regarding the issues they consider to be barriers to successful treatment of adolescent T2DM. Methods: An electronic questionnaire was administered to 220 physicians and nurses attending a conference on pediatric diabetology in 2001. Results: The issues that were most strongly perceived as barriers to successful treatment of adolescents with T2DM were prevalence of high‐risk lifestyle in other family members (98%), lack of immediate risk to life reducing patient motivation (89%), lack of guidelines regarding optimal treatment (73%), prevalence of behavioral and/or psychiatric disorders (71%), and cultural/language barriers (65%). The survey also revealed that in the majority of clinics, T2DM education programs were not designed specifically for type 2 patients nor delivered by a specifically trained education team. Furthermore, despite the fact that cultural and ethnic differences were identified as important barriers to care, educational materials designed for particular racial and cultural groups were used in only 37% of the clinics. Conclusions: This survey identifies a number of areas perceived by clinicians to be significant barriers to successful treatment of T2DM in adolescent patients. Given the multiple challenges identified by the survey, programs addressed specifically to the characteristics of adolescents with T2DM will be necessary, including materials appropriate to the developmental stage and ethnic background of patients.     

Insulin resistance and metabolic syndrome in children of parents with diabetes mellitus

The aim of this prospective study was to research features of insulin resistance and metabolic syndrome in offspring of diabetic parents and to find out whether there is a risk of developing type 2 diabetes mellitus (DM) in these children. Study participants were 30 children of parents with type 1 DM (DM1) (Group I) and 11 children of parents with type 2 DM (DM2) (Group II) who were being followed up in the Diabetes Department of Haseki Research and Training Hospital. The results were compared with a control group of 17 children in the same age group (Group III). There were no statistically significant differences between the Group I and the control group in fasting blood glucose, oral glucose tolerance test values, 1st 2nd and hour insulin, homeostasis model assessment (HOMA) values, body mass index (BMI), systolic and diastolic blood pressure, and lipid parameters, i.e. HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, total cholesterol, and triglycerides. Fasting, 1st and 2nd hour blood insulin levels, HOMA values, BMI, and systolic blood pressure values were significantly higher in Group II compared to the control group (p < 0.05). There were no statistically significant differences between Group II and the control group in lipid parameters, fasting blood glucose, OGTT values, or diastolic blood pressure. We conclude that in our population there is a tendency of insulin resistance and metabolic syndrome in the offspring of parents with DM2, and a risk for developing DM2. Thus, children of patients with DM2 should be followed up so as to recognize early metabolic defects of glucose metabolism and to plan effective preventive efforts to reduce cardiovascular and atherosclerotic risk factors.     

Mauriac syndrome: growth failure and type 1 diabetes mellitus

Growth failure in Type 1 Diabetes Mellitus (T1DM) can occur for several reasons. Mauriac syndrome is a rare cause of severe growth failure in T1DM. There may be different forms and etiologies involved in Mauriac syndrome. However, there are common features noted in these patients. We have compiled a review of cases reported in English in the last 30 years. With adequate insulin treatment there is reversal of growth failure and hepatomegaly if present. However, overly aggressive insulin delivery could result in rapid deterioration of diabetic retinopathy and nephropathy. Close monitoring of growth and pubertal maturation in children with T1DM is essential.     

Hyperglycemic hyperosmolar nonketotic syndrome

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed till recently. Now it is being diagnosed with increasing frequency in obese children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go up, given global increase in incidence of childhood obesity, increased insulin resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality and dehydration without accumulation of β-hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by the ability of the pancreas, to secrete small amount of insulin. Prolonged phase of osmotic diuresis leads to severe depletion of body water, which excees that of sodium, resulting in hypertonic dehydration. These children, usually obese adolescents with T2 DM, present with signs of severe dehydration and depressed mental status but continue to have increased rather than decreased urine output and are at increased risk of developing rhabdomyolysis and malignant hyperthermia. Emergency treatment is directed at restoration of the intravascular volume, followed by correction of deficits of fluid and electrolyte (Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺, PO4⁺⁺), hyperglycemia and serum hyperosmolarity, and a thorough search for conditions that may lead to this metabolic decompensation and their treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic stabilization initially, followed by 0.45% saline with insulin infusion at the rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of insulin infusion once the blood glucose is 250 to 300 mg/dl is generally recommended. However, evidence-based guidelines about composition and tonicity of fluids and electrolyte solutions for early resuscitation and rehydration, the rate of infusion—rapid vs slow, and insulin dose—low vs normal, in treatment of HHNS in children are awaited. Careful monitoring of glucose levels and ensuring adequate hydration in patients ‘at risk’ of HHNS, including those receiving medications that interfere with the secretion or effectiveness of insulin should decrease the risk of HHNS.     

Effect of metformin and rosiglitazone in a prepubertal boy with Alström syndrome

Alstr?m syndrome (AS) is an autosomal recessive disorder characterized by progressive pigmentary retinopathy, sensorineural hearing loss, fatty liver infiltration, obesity, insulin resistance and early-onset type 2 diabetes mellitus (DM2). Early onset of insulin resistance and DM2 are key components of this syndrome. AIM: To study the effect of early initiation of the insulin sensitizer metformin combined with rosiglitazone in a patient with AS with impaired glucose tolerance. PATIENT: An 8 year-old boy with AS presented with acanthosis nigricans and insulin resistance at the age of 6 years. He had progressive excessive weight gain from 9 months of age. By the age of 1 year he developed photosensitivity, blindness and nystagmus. At the age of 5.5 years, his body mass index (BMI) was above the 95th percentile. He developed impaired glucose tolerance at 6 years of age and treatment with metformin was initiated. After 8 months of treatment with metformin he developed DM2. The dose of metformin was increased, and rosiglitazone added. METHODS: A 2-hour oral glucose tolerance test (OGTT) and a rapid intravenous glucose tolerance test (IVGTT) were performed before treatment was initiated, after treatment with metformin and at the end of 1 year of combination therapy with metformin and rosiglitazone to calculate quantitative insulin sensitivity check index (QUICKI) and acute insulin response (AIR). For mutation analysis, all exons and splice site sequences of the ALMS1 gene were amplified and sequenced. RESULTS: Metformin treatment alone at the stage of impaired glucose tolerance did not prevent progression to DM2. However, metformin at a higher dose and in combination with rosiglitazone resulted in improvement of pancreatic beta-cell function, shown by markedly improved first-phase insulin response to glucose measured by AIR. The patient was found to have two heterozygous nonsense mutations in ALMS1, 8008 C-->T Ter, R2670X, and 11449 C-->T Ter, Q3817X. These alterations cause premature stops and result in a truncated ALMS1 protein. CONCLUSION: We suggest that early initiation of combined therapy comprising a high dose of metformin plus rosiglitazone may be valuable in managing insulin resistance and DM2 in children with AS.     

Genes with linkage or association with type 2 diabetes mellitus

Complex diseases, such as type 2 diabetes mellitus (T2DM), arise from metabolic disruptions with genetic and environmental components. Multiple genes are responsible for the genetic susceptibility to T2DM. The contribution of these genes to the diabetic phenotype may be modest, variable among different populations, and dependent on interactions with other genes and the environment. The methods of genetic dissection based on linkage, allele sharing, and linkage disequilibrium may lack the statistical power to detect weak associations in heterogeneous populations. Nevertheless, genes involved in insulin signaling, insulin secretion, insulin resistance, glucose metabolism, obesity, diabetes comorbidity and the hormone processing protease genes have been associated with T2DM. New research strategies are improving the methods of genetic dissection and include genomic sequence information to characterize profiles of sequence variants that predispose to T2DM.     

Impaired beta-cell and alpha-cell function in African-American children with type 2 diabetes mellitus--"Flatbush diabetes"

The incidence of type 2 diabetes mellitus (T2DM) in children and adolescents has substantially increased over the past decade. This is attributed to obesity, insulin resistance and deficient beta-cell function. In children a pubertal increase in insulin resistance and an inability to mount an adequate beta-cell insulin response results in hyperglycemia. Adults with T2DM have a diminished first phase response to intravenous glucose and a delayed early insulin response to oral glucose. Long-term studies show progressive loss of beta-cell function in T2DM in adults; however, such long-term studies are not available in children. To characterize beta- and alpha-cell function in African-American adolescents with established T2DM, we used mixed meal, intravenous glucagon and oral glucose tolerance testing and compared them to obese non-diabetic controls. T2DM was defined as fasting C-peptide >0.232 nmol/l and absent autoimmune markers. BETA-CELL FUNCTION: Meal testing in 24 children and adolescents with T2DM, mean age 14 years, BMI 30 kg/m2, Tanner stage II-V, HbA1c 8.9%, were compared with BMI- and age-matched controls. Forty percent presented with DKA. Half were treated with insulin and half with diet/oral anti-diabetic agents. Although absolute C-peptide response in both groups was similar, the incremental rise in C-peptide relative to plasma glucose in the patients with T2DM compared to controls was 40% and 35% lower 30 and 60 min after the meal, p <0.007 and p <0.026. Glucagon testing in 20 pediatric patients with T2DM compared with 15 matched controls showed significantly lower 6 min stimulated C-peptide relative to the ambient plasma glucose in patients with T2DM compared to controls (0.039 +/- 0.026 vs 0.062 +/- 0.033, p <0.05). The clinical utility is that 78% of patients with a 6 min C-peptide <1.4 nmol required insulin, while 81% of those >1.4 nmol required oral anti-diabetic agents, p <0.0001. Furthermore, the duration of T2DM up to 5 years after diagnosis was associated with lower fasting and glucagon-stimulated C-peptide levels, implying worsening beta-cell function over time, even in children and adolescents. ALPHA-CELL FUNCTION: During meal testing, children and adolescents with T2DM had less suppression of plasma glucagon than non-diabetic controls; this was more severe with longer duration of T2DM and poorer glycemic control. BETA-CELL RECOVERY: In African-American and Hispanic adults, intensive treatment of blood glucose may achieve beta-cell recovery with 35-40% of newly diagnosed patients going into remission after 6 months treatment. They remain off anti-diabetic pharmacological agents in remission for a median of over 3 years with normal HbA1c levels. We hypothesize this to be due to removal of a critical component of glucose or lipotoxicity at the level of the beta-cell and/or peripheral tissue. Four of 20 African-American children presenting with mean glucose 650 mg/dl maintained normal HbA1c levels on small doses of metformin after initial treatment with multiple insulin injections with or without metformin. This suggests a marked recovery of beta-cell function, similar to that in adults. SUMMARY: T2DM in children, as in adults, is characterized by insulin deficiency relative to insulin resistance. Plasma C-peptide levels may be clinically useful in guiding therapeutic choices, since patients with lower levels required insulin treatment; beta-cell function is also diminished with longer duration of T2DM. The possibility exists that in children, as in adults, intensive glycemic regulation may allow for beta-cell recovery and preservation. Thus, optimum beta- and alpha-cell function are central to the prevention of DM and maintenance of good glycemic control in African-American and Hispanic children and adolescents with T2DM.     

Diabetes mellitus in Asian Indian children and adolescents

AIM: To study the clinical and metabolic profile of type 1 and type 2 diabetes mellitus in children and adolescents in a South Asian population. RESEARCH DESIGN AND METHODS: Sixty children were recruited. They were divided into three groups: Group I--type 2 diabetes mellitus (DM2), Group II--type 1 diabetes mellitus (DM1), and Group III--healthy controls. The clinical history and biochemical parameters (HbA1c, serum insulin, C-peptide, triglycerides, total cholesterol and HDL-cholesterol) were recorded. Homeostasis model assessment for insulin resistance (HOMAIR) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS AND CONCLUSIONS: Children and adolescents with DM2 had a significant family history of DM and clinical features of insulin resistance, including increased body mass index, waist:hip ratio and acanthosis nigricans. They also had decreased insulin sensitivity together with dyslipidemia of metabolic syndrome, i.e. high triglyceride, high total cholesterol and low HDL-cholesterol. The presence of these predictors of cardiovascular disorders is known to contribute to morbidity and mortality. Hence, DM2 needs to be recognized early in Asian Indian children.     

Type 2 Diabetes Mellitus in Children and Youth

Type 2 diabetes mellitus (T2DM) which used to be a disease of adults is now seen commonly at an early age in children and adolescents. T2DM is now an important diagnostic consideration in children who present with signs and symptoms of diabetes. The emerging epidemic of obesity in children throughout the world and the resultant insulin resistance contributes to the increasing prevalence of T2DM in this population. The recommended treatment options include metformin and insulin. Optimal glycemic control is essential considering the lifelong nature of the disease and therefore, the increased risk of long term complications – both microvascular and macrovascular. This review article summarizes the classification, diagnosis, pathogenesis, management, complications and screening of T2DM in children, incorporating and contextualizing guidelines from various professional associations.     

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.     

Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates

The pathophysiology of type 2 diabetes (T2DM) involves insulin resistance and relative insulin deficiency in at-risk youth. We-report longitudinal changes in insulin sensitivity and secretion in a high-risk African-American youth with obesity and polycystic ovary syndrome who progressed from normal glucose tolerance to impaired glucose tolerance to T2DM within 5 yr. This report demonstrates that in our patient: (i) insulin resistance was the pre-existing abnormality, but it was the marked decline in insulin secretion which led to T2DM and (ii) surrogate estimates of insulin sensitivity using fasting glucose and insulin concentrations were not reliable indices in reflecting the changes in in vivo insulin sensitivity in this case.     

Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes

Despite the increased prevalence of type 2 diabetes mellitus (T2DM) in the pediatric population, there is limited information about the relative effectiveness of treatment approaches. This article describes the rationale and design of a National Institutes of Health-sponsored multi-site, randomized, parallel group clinical trial designed to test the hypothesis that aggressive reduction in insulin resistance early in the course of T2DM is beneficial for prolongation of glycemic control, as well as improvement in associated abnormalities and risk factors. Specifically, the trial compares treatment with metformin with two alternate approaches, one pharmacologic (combining metformin treatment with rosiglitazone) and one combining metformin with an intensive lifestyle intervention program. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study recruits 800 patients over a 4-yr period and follows them for a minimum of 2 yr and maximum of 6 yr. Patients are 10-17 yr of age, within 2 yr of diagnosis of diabetes at the time of randomization, lack evidence of autoimmunity, and have sustained C-peptide secretion. The primary outcome is time to loss of glycemic control, defined as a hemoglobin A1c >8% for 6 consecutive months. Secondary outcomes include the effect of the alternative treatments on insulin secretion and resistance, body composition, nutrition, physical activity and fitness, cardiovascular risk monitoring, microvascular complications, quality of life, depression, eating pathology, and resource utilization. TODAY is the first large-scale, systematic study of treatment effectiveness for T2DM in youth. When successfully completed, this study will provide critical new information regarding the natural history of T2DM in youth, the benefits of initiating early aggressive treatment in these patients, and the efficacy of delivering an intensive and sustained lifestyle intervention to children with T2DM.     

IAP National Task Force for Childhood Prevention of Adult Diseases: insulin resistance and Type 2 diabetes mellitus in childhood

Type 2 diabetes mellitus (DM) has traditionally been considered a disease of adults. However, in the last 2 decades, it is increasingly being reported in children and adolescents. Obesity is a strong correlate, and the increasing prevalence of obesity and poor physical activity is precipitating type 2 DM at younger ages in the ethnic groups at risk.Indians and other South Asians are among the ethnic groups particularly prone to insulin resistance and type 2 DM, the other racial groups being some American Indian tribes like the Pima Indians, Mexican Americans,Pacific Islanders and African Americans,among others. The WHO has predicted that India will have the greatest number of diabetic individuals in the world by the year 2025.Type 2 DM starting during adolescence puts the individual at risk for major morbidity and even mortality right during the productive years of life. The microvascular complications of DM (nephropathy, retinopathy, neuropathy) are brought on at an early age. In addition, type 2 DM and obesity are two components of a metabolic syndrome of insulin resistance, the other features of which include hypertension, dyslipidemia and hypercoagulability of blood. All these conditions together increase the risk for cardiovascular and cerebrovascular mortality and morbidity (i.e., myocardial infarction and stroke). The resulting economic burden will be enormous.Type 2 DM and the insulin resistance syndrome are to a large extent preventable.Adoption of a healthy eating and physical activity pattern has resulted in decreasing the development of DM in a few recent studies from various parts of the world. A concerted,multi-pronged effort is needed, involving the general public, pediatricians and general physicians, teachers and schools, the media,the government and professional medical bodies, to generate a momentum towards the goal of prevention of type 2 DM and the insulin resistance syndrome in the young population of India.     

Arterial thrombosis resulting in amputation in a child with poorly controlled type 1 diabetes and heterozygous Factor V Leiden mutation

Children with venous thromboses have greater than 50% likelihood of carrying a genetic thrombophilic defect, and two-thirds of such defects will be a mutation in the factor V gene referred to as Factor V Leiden. Poorly controlled type 1 diabetes mellitus (T1DM) increases the risk for thrombosis. We report a massive arterial thrombosis resulting in unilateral below-the-knee amputation in a 12-yr-old white girl with a heterozygous Factor V Leiden mutation and a 2-yr history of poorly controlled T1DM. This report emphasizes the need to test for thrombophilic defects in children with thrombosis or with a family history of thrombosis. Good metabolic control is especially important in children with T1DM and known thrombophilic defects.     

Addison's disease presenting in four adolescents with type 1 diabetes

Primary adrenocortical insufficiency (Addison's disease) is a potentially fatal condition that often develops insidiously and can be easily overlooked. Although rare in the general population, it is more common in patients with type 1 diabetes mellitus (T1DM). The combination of Addison's disease with T1DM and/or autoimmune thyroid disease is known as autoimmune polyendocrine syndrome type-2 (APS-2). T1DM commonly precedes the development of adrenocortical insufficiency in most patients with APS-2. We, in this study, present four cases of Addison's disease developing in adolescents with pre-existing T1DM. Risk factors for Addison's disease in this population include a history of other organ-specific autoimmunity, particularly thyroid, and a positive family history. In addition to the 'classic' Addisonian features, the development of unexplained recurrent hypoglycemia, reduction in total insulin requirement, improvement in glycemic control, or abnormal pigmentation should arouse suspicion of adrenocortical insufficiency. Adrenal antibodies have been proposed as a screening tool for Addison's disease in the T1DM population, but doubts remain about their specificity and sensitivity. The addition of specific HLA DRB1 subtyping has been proposed to improve predictive value.     

21-hydroxylase autoantibody-negative Addison's disease in a 5-year-old boy with adrenal crisis and type 1 diabetes mellitus

Patients with type 1 diabetes mellitus (T1DM) have an increased risk of other autoimmune disorders. The combination of Addison's disease with T1DM and/or autoimmune thyroid disease is known as autoimmune polyendocrinopathy type 2 (APS-2). 21-hydroxylase autoantibody (21OHAb) is considered as a valuable marker for identifying patients with autoimmune Addison's disease (AD); however, it is not available in some countries. Here we present a 5-year-old boy with newly diagnosed T1DM, who developed AD with adrenal crisis within only six months, and after 1-year treatment, the test of 21OHAb was negative. This was a rare and the first APS-2 case in Taiwan, because APS-2 affects female adults more often, but not boys. At diagnosis of T1DM, we suggest that checking diurnal cortisol and adrenocorticotropic hormone levels as a baseline evaluations, and if it is available, checking 21OHAb as well. If there is subtle evidence of AD, such as unexplained hypoglycemia or unreasonably reduced insulin requirements, adrenal functions must be studied as soon as possible, even in the 21OHAb-negative T1DM patients. Even if nothing is abnormal, the patient still needs an annual measurement.     

Epilepsy in children with type 1 diabetes mellitus: Pathophysiological basis and clinical hallmarks

We provide an overview on the current knowledge about the association between epilepsy and type 1 diabetes mellitus (T1DM). People with T1DM have a 2–6-fold higher risk of epilepsy than the general population. The onset of T1DM anticipates the onset of epilepsy by a mean period between 1,5 and 2,8 years. These two disorders share four potential distinct pathogenic factors: a) genetic predisposition; b) factors involved in autoimmune responses (i.e. anti-glutamic acid decarboxylase antibodies-GADAbs); c) effects of hypo/hyperglycaemia; d) cerebrovascular damages resulting in ischaemic processes.Seizures semiology prominently includes focal (up to patterns of epilepsia partialis continua) or secondarily generalized seizures but also reflex seizures and various forms of generalized seizures. EEG abnormalities are more common in people with an inappropriate metabolic control with a prominent involvement of fronto-temporal regions.Epilepsy management does not differ between patients with and without diabetes and insulin, nutritional recommendations and physical activity may also produce significant benefits on seizures control. Possible therapeutic alternatives in selected cases include immunosuppressive drugs (in patients with GADAbs) and ketogenic diet.