Global epidemiology and burden of type 2 diabetes mellitus in children and young adults

The growing pandemic of childhood obesity has led to marked increases in the incidence and prevalence of type 2 diabetes mellitus (DM) and has further complicated the differentiation between type 2 and type 1 DM because more children with type 1 DM are overweight at time of diagnosis. In addition, numerous studies have demonstrated β-cell autoimmunity in children with type 2 DM. (1)After completing this article, readers should be able to:Type 2 diabetes mellitus (DM), historically considered a serious chronic medical condition only for older individuals, now has an increased prevalence in children and adolescents. The estimated overall incidence of type 2 DM is 22 cases per 100,000 youth or approximately 3600 youth diagnosed with the condition each year. (2) From a public health perspective, DM is the seventh leading cause of death in the United States, a figure that is likely underestimated. (3) The total cost to treat DM in both adults and children is approximately $174 billion per year, and medical expenses for individuals with diagnosed DM are 2.3 times higher than for those without DM. (3) The clinical and financial burdens of DM are increased by the complications and comorbidities of the disease. Because complications of DM develop and worsen during the disease, (2) it is important to effectively recognize and manage type 2 DM early when it is diagnosed during childhood and adolescence.DM represents a group of endocrine disorders characterized by hyperglycemia caused by defective insulin secretion, defective insulin action, or both. (4) The original division into 2 types was based on age at presentation and dependence on insulin. Now categories of DM (Table 1) are differentiated by their known underlying pathophysiologic characteristics. All forms of DM ultimately lead to hyperglycemia, although there may be overlap in the fundamental pathologic processes in each patient.Recent epidemiologic studies have demonstrated that more than 20% of new cases of DM in children and adolescents are due to type 2 DM. (5) The incidence of type 2 DM in children has increased in part because of the epidemic of childhood obesity and the associated insulin resistance, although the actual incidence of type 2 DM in children is likely higher than reported because of underdiagnosis.The incidence of type 2 DM increases with age. The SEARCH for Diabetes in Youth study demonstrated that the incidence of type 2 DM in children age 10 to 19 years was 42 per 100,000 youth compared with 1 in 100,000 youth among children age 0 to 9 years. (2) The peak age at onset of type 2 DM in children coincides with pubertal timing because the mean age at diagnosis is 12 to 16 years. (6) Females have a higher incidence of type 2 DM than males, (5) likely because girls are more insulin resistant and carry more subcutaneous fat than boys. (7)Type 2 DM disproportionately affects racial and ethnic minorities. American Indian youth have the highest incidence at 174 per 100,000. Black youth also have a particularly high incidence of 105 per 100,000 compared with 19 per 100,000 in non-Hispanic whites. (2)Epidemiologic studies report that children born to mothers with gestational diabetes are at greater risk of developing type 2 DM. (8) Breastfeeding appears to have protective effects against the development of type 2 DM. (9)The cause of type 2 DM is multifactorial, but the high concordance rate among monozygotic twins (1) and the frequent association with a family history of DM (10) suggest a genetic component. Between 74% and 100% of patients with type 2 DM have a first- or second-degree relative with the disease, in contrast to only 5% of patients with type 1 DM with a family history of type 1 DM. (6) Recent studies have identified multiple genetic loci that are associated with higher risk of type 2 DM. For example, polymorphisms in the TCF7L2 gene result in impaired insulin secretion and defective insulin processing, which confer a 1.4 times increased risk of type 2 DM. (1) More genetic markers are being identified with improvements in genetic testing.Glucose metabolism is tightly regulated by several processes, including sensing of glucose concentration, insulin synthesis, and secretion by pancreatic β-cells; suppression of hepatic glucose output; and insulin action on stimulated glucose uptake by the liver, intestines, and skeletal muscle. Hyperglycemia can result from derangements in any of these processes.Typically, type 1 DM and type 2 DM are conceptualized on a spectrum. Type 1 DM results from immune-mediated destruction of β-cells, leading to insulinopenia. Type 2 DM is the result of obesity-mediated insulin resistance and non–immune-mediated deficiency in insulin secretion.The pathogenesis of type 2 DM is complex and involves interactions between genetic and environmental factors. The core defect is varying degrees of insulin resistance and subsequent progressive insulinopenia. Other factors associated with obesity, such as elevated plasma free fatty acid concentrations and increased inflammatory markers, further inhibit β-cell insulin production and insulin-mediated glucose uptake. This leads to a cycle of worsening hyperglycemia and further metabolic derangement.A theory called the accelerator hypothesis suggests that obesity and weight gain contribute significantly to β-cell stress and confer earlier onset of all types of DM. Obesity is increasingly being accepted as a contributor to β-cell failure in genetically susceptible children, and increasing evidence suggests the influence of obesity in abnormal immune modulation. (1)During the past 30 years Americans have increased their total caloric intake by an additional 300 kcal/d. (11) Consumption of juices and sugar-sweetened beverages is a major source of these additional calories in the diet of children and adolescents (12) and is strongly associated with an increased risk of obesity and type 2 DM. (7) In addition, fewer children and adolescents are participating in recommended levels of physical activity.The association between lower birth weight and type 2 DM suggests that in utero programming may increase the risk of type 2 DM. (13) A thrifty-phenotype hypothesis suggests that poor fetal nutrition produces a postnatal metabolism that is adapted to poor but not plentiful nutrition. This programming contributes to insulin resistance and can predispose the development of type 2 DM in the context of excess nutrition and obesity. (14)Because up to 24% of children and adolescents with type 1 DM are overweight at diagnosis, (6) differentiating between type 2 DM and type 1 DM has become more difficult. (15) Further complicating the clinical delineation is the presence or absence of autoimmunity. The SEARCH for Diabetes in Youth Study measured the presence of glutamic decarboxylase (GAD) antibodies among diabetic patients. Positive GAD antibodies were found in 21% of patients with type 2 DM older than 10 years. (5) The Treatment Options for Type 2 DM in Adolescents and Youth (TODAY) study, a multicenter clinical trial, evaluated the presence of GAD and insulinoma-associated protein 2 antibodies. Of patients with diagnosed type 2 DM, 9.8% were antibody positive, 5.9% were positive for a single antibody, and 3.9% were positive for both antibodies. Those patients diagnosed as having type 2 DM who were antibody positive were more likely to be white and male and had a lower body mass index than antibody-negative patients. (16) A significant controversy exists regarding the classification of antibody-positive type 2 DM, with many authors maintaining that antibody-positive type 2 DM should be considered early type 1 DM and treated as such.The presenting symptoms of type 1 and type 2 DM can be similar and include polyuria, polydipsia, and polyphagia. Weight loss can be present in both types of DM. Clinical signs to suggest type 2 DM include overweight body habitus, with more than 85% of children with type 2 DM considered overweight or obese at the time of diagnosis. (6) Acanthosis nigricans, a darkened, thick, velvety appearance to the skin found typically in folds or creases, is present in 90% of patients with type 2 DM and can be the most easily visible clinical indicator of insulin resistance. (7) The frequency of acanthosis nigricans in obese adolescents or hyperinsulinemic children varies considerably by ethnicity. Up to 90% of obese or hyperinsulinemic children in Native American populations had acanthosis nigricans, whereas it was present in less than 5% of non-Hispanic white counterparts. (7) Clinicians can look for acanthosis nigricans in the nape of the neck, axilla, groin, and over flexor surfaces. The presence of ketoacidosis, normally found in patients with type 1 DM, does not rule out type 2 DM. Some reports indicate that up to 25% of children and adolescents with type 2 DM present with diabetic ketoacidosis. (17)Type 2 DM generally has a more insidious onset than type 1 DM, and many patients may be asymptomatic at presentation. However, because of the potentially long-standing hyperglycemia, patients may already have evidence of microvascular and macrovascular complications at the time of diagnosis. (10)Overall, the clinical distinction between type 1 DM and type 2 DM is increasingly obscured, especially with the increasing obesity pandemic. Clinicians must weigh the evidence to support their diagnosis and consider the potential outcomes of misclassification. In the case of significant hyperglycemia, diabetic ketoacidosis, and/or positive antibodies, it may be prudent to treat patients as having type 1 DM and wean insulin therapy if the future clinical course dictates.The criteria for diagnosis of DM were based on data to delineate risk for the development of retinopathy, a microvascular complication of DM, and are included in Table 2. (10) In 2009, an international expert committee convened and added an additional criterion for diagnosis, a hemoglobin A1c (HbA1c) level greater than 6.5% (0.07). (10)Indications to test for type 2 DM according to the Type 2 DM Consensus Panel are given in Table 3. Testing should begin at age 10 years or at the age of pubertal onset, whichever comes first, and should be repeated every 3 years. (18) The preferred method is to measure a fasting plasma glucose level, but a 2-hour plasma glucose level measured during an oral glucose tolerance test (OGTT) can be an alternative. (6)The American Diabetes Association (ADA) recommends that treatment of all children with DM should include routine follow-up every 3 months with a diabetes care team. (18) This team should include nutritional, psychological, and educational support and a medical professional experienced with DM care. The patient's self-management involves monitoring of blood glucose level, medication compliance, attention to dietary intake, and physical activity. Psychosocial considerations and medical compliance must also be addressed to ensure optimal success with therapy. The HbA1c level should be measured every 3 months during outpatient visits, and the goal HbA1c should be less than 7%. (18)(19)(20) Assessment of lipids, liver function tests, microalbuminuria, and signs and symptoms of sleep apnea should occur at diagnosis and annually. (19) Coordination between the diabetes care team and the primary care practitioner ensures a complete medical home for the child or adolescent.Treatment should be guided by the acuity of the clinical presentation. If a patient is acutely ketotic, dehydrated, or acidotic, intravenous hydration and insulin administration with inpatient admission are warranted. If the presentation is less acute, subspecialty referral, outpatient education, and use of oral medications can be initiated. Once the patient is clinically stable, treatment of type 2 DM is dually focused on weight management and minimizing complications associated with hyperglycemia.Lifestyle modification is an essential component of the management of type 2 DM and includes an emphasis on proper diet and exercise to maintain a healthy weight while preserving linear growth. For optimal management, lifestyle modification should be centered around the family unit and not strictly on individual patients. (20)Pharmacologic therapy addresses various aspects of the pathogenesis of type 2 DM (Figure) by reducing insulin resistance, increasing insulin secretion, slowing postprandial glucose absorption, or supplementing inadequate secretion of insulin. Metformin, a biguanide, is the only US Food and Drug Administration (FDA)–approved oral medication for treatment of type 2 DM in children older than 10 years and is considered first-line therapy in nonacute presentations. The mechanism of action is to decrease hepatic glucose production and enhance insulin-mediated glucose uptake in muscle and adipose cells. Adverse effects include transient abdominal pain, diarrhea, and nausea, although it is generally well tolerated. Metformin should not be given to patients with renal insufficiency, liver disease, or cardiac or respiratory insufficiency. Patients should be warned to discontinue metformin therapy before receiving intravenous contrast for radiographic studies because of the increased risk of lactic acidosis. In adults there is evidence that metformin can normalize blood glucose levels, decrease cholesterol levels, and reduce hypertension. Metformin can also be used to normalize ovulatory abnormalities in patients with polycystic ovarian syndrome. It is available in a liquid formulation and as an extended-release formulation, which can aid compliance and potentially reduce adverse effects. The recommended starting dose for metformin is 500 mg given orally once daily, with a maximum dose of 2000 mg per day.Insulin is used to attain early normalization of glycemic control, especially in patients who are acutely ill or have significant hyperglycemia, and insulin therapy should be started in all patients who present with diabetic ketoacidosis. Recent American Academy of Pediatrics clinical practice guidelines on the management of newly diagnosed type 2 DM recommend that insulin therapy be initiated in patients who have a random blood glucose level greater than 250 mg/dL (13.9 mmol/L) or whose HbA1c level is greater than 9%. (20) Once the diagnosis of type 2 DM is determined, insulin therapy can often be reduced as metformin therapy is initiated. Adverse effects of insulin can include weight gain from its anabolic effect on metabolism. Hypoglycemia, a potential adverse effect, is not as common among patients with type 2 DM.Other therapies, although not FDA approved for patients younger than 18 years, can be used by the diabetes management team to improve glycemic control. Sulfonylureas (glyburide, glipizide, and glimepiride) directly increase insulin secretion, so they are most useful when there is residual β-cell function. Major adverse effects include hypoglycemia and weight gain. Glucosidase inhibitors (acarbose and miglitol) reduce absorption of carbohydrates in the upper small intestine. They can lower HbA1c levels by 0.5% to 1%, and the major adverse effects are gastrointestinal intolerance and flatulence. Incretins (exenatide) are designed to increase postprandial insulin secretion. Exenatide is administered as a twice-daily injection. Adverse effects include nausea, vomiting, diarrhea, dyspepsia, jitteriness, dizziness, headaches, and hypoglycemia, especially if given with a sulfonylurea. Thiazolidinediones (rosiglitazone and pioglitazone) increase insulin sensitivity in muscle, adipose tissue, and the liver. In isolation, they can reduce HbA1c levels by 0.5% to 1.3%. Results from the TODAY study demonstrated that metformin in combination with rosiglitazone was more successful than metformin alone or metformin with lifestyle modification in preventing an increase in HbA1c levels above 8% (0.08). (20) There is some evidence that this combination may improve lipid profiles by lowering triglyceride levels and increasing high-density lipoprotein levels. (21) Adverse effects include edema, weight gain, and anemia and may infer additional cardiac risk (Figure).The risk of DM-related complications is directly related to the duration of disease. Prompt diagnosis and appropriate therapy are paramount in reducing this risk. Because of its insidious onset, many patients with type 2 DM have evidence of complications at the time of diagnosis. Among a sample of 100 Pima Indians with type 2 DM, 18% had hypertension, 7% had dyslipidemia, and 22% had microalbuminuria at the time of diagnosis. (22) Microvascular complications of type 2 DM include nephropathy, retinopathy, and neuropathy. Macrovascular complications include hypertension and hyperlipidemia, which can lead to cardiovascular disease. The ADA recommends that patients with type 2 DM have blood pressure measurements performed at every routine diabetes visit. (18) In the UK Prospective Diabetes Study, hypertension was found to be a more significant predictor of cardiovascular disease than blood glucose control. This study also found a 25% reduction in the risk of microvascular complications when the average HbA1c level decreased from 7.9% to 7.0%. (23)Patients should be screened for retinopathy with a dilated eye examination near the time of diagnosis and then yearly afterward. A lipid profile should be performed shortly after diagnosis, once glycemic control is attained, and should be performed annually thereafter. Urine microalbumin should be measured at diagnosis to assess for early nephropathy and followed up yearly. (18)Primary public health prevention efforts should target the general population to limit the prevalence of obesity. Secondary prevention should focus on screening those children who are at high risk for the development of type 2 DM (Table 2). Tertiary prevention in patients with type 2 DM should address reduction of complications.The authors wish to acknowledge Babalola Faseru, MD, MPH, assistant professor, Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, and Naim Mitre, MD, Naim Mitre, MD, medical director of clinical services, assistant fellowship program director, assistant professor of pediatrics, Division of Endocrine/Diabetes, Department of Pediatrics, University of Missouri-Kansas City/Children's Mercy Hospital.

On the basis of strong research evidence and consensus, type 1 diabetes mellitus (DM) remains the most common form of DM in children and adolescents. The incidence of type 2 DM in the pediatric population is rapidly increasing because of the obesity epidemic, and minority groups are disproportionately affected. (2) (10) (19) On the basis of some research evidence and consensus, it can be challenging to initially differentiate between type 2 DM and type 1 DM clinically because of the increased prevalence of obesity, the complex interplay of autoimmunity and obesity, and common symptoms at presentation. (1) (10) (19) Significant evidence and consensus support a genetic basis for the development of type 2 DM in children. Physicians should routinely screen at risk children older than age 10 years for DM. Screening criteria include obesity, a family history of type 2 DM, a minority racial or ethnic background, acanthosis nigricans, or other diseases associated with insulin resistance, including polycystic ovary syndrome, hypertension, or dyslipidemia. (1) (10) (18) (19) On the basis of consensus, diagnosis of type 2 DM can be confirmed by an elevated fasting blood glucose level greater than 126 mg/dl (7.0 mmol/L), an elevated 2-hour plasma glucose greater than 200 mg/dL (11.1 mmol/L) on an oral glucose tolerance test, an elevated random blood glucose greater than 200 mg/dL (11.1 mmol/L), or a hemoglobin A1c level greater than 6.5% with suggestive symptoms. (10) According to strong research evidence and consensus, once the diagnosis has been made, treatment should be based on the acuity of presentation and should focus on lifestyle modification and on normalizing hyperglycemia to minimize complications. Metformin is currently first-line treatment for type 2 DM in children and adolescents older than age 10 years who present nonacutely. (18) (19) Strong research evidence and consensus demonstrate that because type 2 DM has an insidious onset, microvascular and macrovascular complications can be present at the time of diagnosis. Patients should be screened for the presence of complications when the diagnosis of type 2 DM is made and in follow-up. (6) (10).

There have been numerous recent reports of case series of type 2 diabetes mellitus (DM) in American Indian, African-American, Hispanic, Asian-American and white children from North America. A similar phenomenon has also been described in several other countries. Prevalence and incidence estimates vary depending on the age and ethnicity of the population, but it is estimated that type 2 DM represents 8-45% of patients with DM currently diagnosed in large US pediatric centers; however, this is likely to be an underestimation and incidence is probably rising. The young patients diagnosed with type 2 DM in the USA were generally overweight, had a strong family history of type 2 DM and often had signs of insulin resistance. The majority belonged to ethnic groups at high risk for type 2 DM. More girls than boys were diagnosed. The few data on follow-up available suggest a high prevalence of microvascular and macrovascular complications among young adults who developed type 2 DM during childhood. Type 2 DM in children has recently been recognized as a potential public health problem in North America. As obesity is currently on the increase in several industrialized or industrializing countries, a similar increase in type 2 DM in children may soon emerge worldwide, and this will require preventative measures.

1. J. Darrell Nesmith, MD, MPH* 1. 2. *Assistant Professor of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR. Objectives After completing this article, readers should be able to: 1. Delineate the population in which type 2 diabetes mellitus is reaching epidemic proportions. 2. List the characteristics of type 2 diabetes mellitus. 3. Explain the increasing prevalence of type 2 diabetes mellitus among children. 4. Characterize the clinical and laboratory features as well as the course of the disease that will assist in classification of the patient who has diabetes mellitus. 5. Describe the treatments for type 2 diabetes mellitus. Type 2 diabetes mellitus (DM) is a common disease affecting more than 15 million Americans. Its prevalence among adults is increasing, but more worrisome is the recent recognition of type 2 DM among children and adolescents. Little is known about the etiology, management, and changing epidemiology of this disease in pediatric populations. Nonetheless, practitioners who care for children and adolescents must consider the diagnosis of type 2 DM in the child presenting with hyperglycemia. The diagnostic criteria and etiologic classification of DM are listed in Tables 1⇓ and 2⇓ . The diagnosis of DM is based on blood glucose measurements that may be obtained randomly, in the fasting state, or during an oral glucose tolerance test. The fasting blood glucose test is easy and inexpensive to perform and is recommended for screening by the American Diabetes Association (ADA). The criteria for making the diagnosis of DM were changed in 1997 by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus to propose simple and sensitive screening tests for carbohydrate metabolism derangements. View this table: Table 1. Criteria for the Diagnosis of Diabetes Mellitus (DM)1 View this table: Table 2. Etiologic Classification of Diabetes Mellitus (DM)1 DM represents a group of diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Type 1 DM is due to insulin deficiency usually caused by autoimmune destruction of …

To review the prevalence of the metabolic syndrome and type 2 diabetes in children and adolescents. Literature review. It is well demonstrated that cardiovascular risk factors are frequent in childhood obesity and they tend to cluster. However, the frequency of the metabolic syndrome in childhood and adolescence has been investigated only by few studies. In spite of the diverse criteria used for defining the metabolic syndrome, it is evident that the syndrome is already highly prevalent among obese children and adolescents. Population-based data suggest that the epidemic of pediatric obesity is being followed by an increase of type 2 diabetes mellitus, especially in the United States and in minorities. For the European countries, there are no population-based incidence and prevalence data concerning type 2 diabetes mellitus in children and adolescents. From the available data, the magnitude of the problem in the European Caucasian population seems to be much less than in North America. There is an urgent need to establish internationally acceptable criteria for the metabolic syndrome in children and adolescents and to commence screening for this syndrome. Although type 2 diabetes mellitus is still rare among European children, screening is recommended for type 2 diabetes mellitus or impaired glucose tolerance in children and especially in adolescents with substantial risk for the development of this disease.

Aim. To study dynamics of main epidemiological characteristics (incidence and prevalence) of type 1 diabetes mellitus (DM) in children in theRussian Federation (RF) and its Federal districts (FD) in 2001-2007. Materials and methods. Analysis of main epidemiological characteristics (incidence, prevalence, mortality) of type 1 DM in children of RF has beenunderway in the Institute of Pediatric Endocrinology, ERC, since 2001 based on results of questionnaire studies. The questionnaires regularly distributedamong Health Committees of RF subjects (primary sources of information) are designed to collect data on the size, age and sex compositionof childrens populations affected by DM1 and the number of newly diagnosed cases as per the end of each reporting year. The data obtainedare compared with those stored in the State Diabetes Registry (secondary source of information). Results. Major trends in the dynamics of epidemiological characteristics of type 1 DM in children of RF are similar to those worldwide. Mean annualgrowth rate is 2,8%. The incidence of DM1 remains highest in the North-West FD (15,66 per 100 000 children) followed by Central andVolga FDs (12,82 and 10,6 respectively) where its is close to the average value FDr RF (11,01). The incidence of DM1 continues to decrease in theSouthern FD (6,61% per year) and undergoes up-and-down fluctuations in Ural and Siberian FDs. It steadily grows in the Far East FD. TheNorth-South gradient of DM1 morbidity across the territory of RF has persisted during the study period. Conclusion. Monitoring main epidemiological characteristics of type 1 diabetes mellitus in children of RF is an integral component of the organizationof medical and preventive aid to these patients that creates a basis for predicting morbidity, planning measures for its control, and improvinggeneral quality of healthcare provided to diabetic children

The incidence of type 2 diabetes mellitus (DM2) in children has increased worldwide and is commonly associated with overweight. Forty-four children with DM2 were studied by clinical histories, anthropometric measurements, and biochemical analysis. Homeostasis model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were determined to evaluate insulin resistance. Only five patients presented normal body mass index (BMI); the remainder were overweight, and 76% had acanthosis nigricans. Laboratory results yielded hyperglycemia, elevated glycosylated hemoglobin, insulin and C-peptide. Elevated HOMA-IR and decreased QUICKI values suggest insulin resistance. No significant difference was found between sexes, although overweight in girls had more influence over blood pressure and lipid levels (p <0.05). Time from diagnosis and HOMA-IR yielded relevant values (p = 0.010). Laboratory results, QUICKI, and HOMA-IR values suggested that these patients present DM2 and decreased insulin sensitivity. We recommend prevention of overweight and sedentary life-style.

To investigate the global, regional, and national burden and risk factors of type 2 diabetes mellitus (T2DM) among older adults aged ≥65 years from 1990 to 2021, with projections to 2040. Using the Global Burden of Disease database, this study analysed global, regional, and national T2DM burden and risk factors across sex, age groups, and Socio-Demographic Index (SDI) levels. Annual percentage changes were calculated, and predictions used a Bayesian age-period-cohort model. Among older adults aged ≥65 years, the global age-standardized prevalence and mortality of T2DM rose by 1.9% and 0.32% per year, respectively, from 1990 to 2021. T2DM's proportion of total disability-adjusted life years (DALYs) and mortality from all diseases increased, as did its share of T2DM cases across all age groups. Mortality rose fastest in the 85-89 group (0.52% annually). High SDI regions exhibited the highest prevalence, whereas lower SDI correlated with higher mortality rates. Eastern Europe and Uzbekistan experienced the fastest DALYs growth. The global burden of T2DM in older adults is projected to continue increasing by 2040. Globally, high body mass index contributed most to T2DM burden, while high temperature and sugar-sweetened beverages (SSBs) showed the fastest-growing DALYs rates. The fastest-growing risk factor in high-SDI regions was sugar-sweetened beverages, while high temperature was the fastest-growing risk in low-SDI regions. Diabetes cases among older adults have tripled globally since 1990 and are projected to keep increasing. Wealthier nations face diet-related risks, while poorer regions are more affected by environmental factors. Region-specific prevention strategies are urgently needed.

1. Dorit Koren, MD, MTR* 2. Lynne L. Levitsky, MD* 1. *Division of Pediatric Endocrinology and Pediatric Diabetes Center, Department of Pediatrics, Massachusetts General Hospital, Boston, MA * Abbreviations: ADA: : American Diabetes Association DKA: : diabetic ketoacidosis FDA: : Food and Drug Administration FPG: : fasting plasma glucose HbA1c: : glycohemoglobin IR: : insulin resistance LGA: : large for gestational age MODY: : maturity-onset diabetes of youth NAFLD: : nonalcoholic fatty liver disease RISE: : Restoring Insulin Secretion SES: : socioeconomic status SGA: : small for gestational age T1D: : type 1 diabetes mellitus T2D: : type 2 diabetes mellitus TODAY: : Treatment Options for Type 2 Diabetes in Adolescents and Youth The incidence and prevalence of type 2 diabetes mellitus (T2D) are increasing in children and adolescents as a result of the worldwide pediatric obesity epidemic. It is important to distinguish type 1 diabetes mellitus, which is more common in children, from T2D because clinical phenotypes may overlap at presentation, but clinical course and treatment options differ considerably. Thus, it is crucial to diagnose this disease early and to choose appropriate treatment. In addition, prevention of T2D by directly addressing and preventing or ameliorating excess weight gain in young people is of great importance in primary care. After completing this article, readers should be able to: 1. Describe the pathophysiology and risk factors for type 2 diabetes mellitus (T2D) in children and adolescents. 2. Explain that there may be an overlap in the presentation between type 1 diabetes mellitus (T1D) and T2D: children with T1D may be overweight or obese, and children with T2D may present with ketosis or ketoacidosis. 3. Screen appropriate childhood populations for T2D. 4. Recognize that individuals with youth-onset T2D are at higher risk for diabetes-related complications than those with T1D and adults with T2D and, therefore, require careful longitudinal follow-up and treatment. The pediatric obesity pandemic of the past few decades has been accompanied by an increase in the incidence and prevalence of type 2 diabetes mellitus (T2D) in childhood, with a disproportionate disease burden in children of minority ethnic groups and low socioeconomic status (SES). (1) Childhood-onset T2D is associated with greater …

Hyperglycemia and Diabetes Mellitus in Children with Pancreatitis

e24101 Background: Diabetes mellitus (DM) has emerged as a possible late sequela after successfully treating pediatric and young adult (YA) malignancies. We conducted a systematic review and meta-analysis in order to quantify this risk and assess possible risk factors. Methods: We searched MEDLINE and EMBASE databases from inception to April 2019. We included cohort or case-control studies that reported the risk of DM (hazard ratio [HR], relative risk, or odds ratio, and 95% confidence interval [CI]) among childhood and YA cancer survivors ( &lt; age 21 years) compared to those without a history of childhood or YA cancer. We used the Newcastle-Ottawa Score (NOS) to assess risk of bias and study quality. Study effect estimates were pooled using random-effects meta-analyses. Heterogeneity was assessed using the I2 statistic. Results: After applying our exclusion/inclusion criteria, we included 6 articles in our meta-analysis, with a median follow-up time of 11 (range 10-23) years. The median NOS score was 8 (range 7 – 8), indicating high study quality. The risk of DM was significantly higher in childhood and YA cancer survivors relative to controls (HR 1.66, 95% CI 1.54 to 1.79, I2 = 1%). Among cancer types, the highest risk for DM was reported after treatment for leukemia (HR 2.91, 95% CI 2.01 to 4.22 I2 = 75%), lymphoma (HR 1.63, 95% CI 1.37 to 1.94, I2 = 0%) and central nervous system malignancies (HR 1.77, 95% CI 1.30 to 2.39, I2 = 49%), relative to controls. Receiving total body irradiation or abdominal radiation was associated with a DM risk of 4.52 (95% CI 2.29 to 8.93, I2 = 87%), relative to controls. Conclusions: Our meta-analysis demonstrated an increased risk of developing DM among childhood and YA cancer survivors. More emphasis on screening for DM and prevention among this population should be offered.

The 125I-C1q binding test for the detection of soluble immune complexes in native unheated human serum was applied to the study of sera from 52 patients with diabetes mellitus in childhood. This radiolabeled C1q binding test is more sensitive and reproducible among the various methods proposed for the detection of immune complexes. The 125I-C1q binding activity in 52 sera from diabetes mellitus in childhood was 9.47 +/- 0.36% compared to 6.94 +/- 0.74% in normal controls. 125I-C1q binding values in diabetes mellitus in childhood were significantly higher than normal controls. Slight high values were seen in 3 patients with positive anti-DNA-antibodies in diabetes mellitus in childhood. 125I-C1q binding was not significantly increased in patients with positive antithyroid antibodies and insulin antibodies. There was no significant correlation between the duration of diabetes and 125I-C1q binding activity.

The epidemiology of type 1 diabetes mellitus may provide insights into the pathogenesis of the disease. The aim of this work was to characterize the trend of the incidence of type 1 diabetes mellitus in Romanian children aged from 0 to 17 years over a 10-year interval. Data regarding new cases were obtained from two sources: (1) The Romanian Childhood Diabetes Registry and (2) Records of the Medical Center "Cristian Serban", Buzias. The demographic data were retrieved from the National Institute for Statistics. The incidence was calculated for the age groups 0-4, 5-9, 10-14, and 15-17 years. A total of 3196 new cases, aged below 18 years, were found by both the sources. There were significant differences between the groups (p=0.012), the mean incidence being highest in the age group 10-14 years (9.6/100,000/year, 95% CI 9-10.1) and lowest in children aged from 0 to 4 years (4.8/100,000/year, 95% CI 4.4-5.3). Boys were slightly more frequently affected than girls (p=0.038). The age and gender adjusted incidence of type 1 diabetes mellitus increased significantly (p<0.001) from 6.2/100,000/year (95% CI 5.5-6.9) in 2002 to 9.3/100,000/year (95% CI 8.4-10.3) in 2011. The raise in incidence was noticed in all age groups except for 15-17 years. Romania is a country with an intermediate incidence of type 1 diabetes mellitus in children, which is slightly higher in boys than in girls. The incidence of type 1 diabetes mellitus increased continuously during the 10-year survey, with the exception of the oldest teens.

The variety of complications of type 1 diabetes mellitus (DM) in children and adolescents are often observed in clinical practice. Among them, damage to the central and peripheral nervous system prevails. The term «peripheral vegetative insufficiency» (PVI) refers to a complex of vegetative manifestations that occur in the peripheral (segmental) part of the VNS against the DM background.&#x0D; Objective — to determine the clinical typology of PVN in children with type 1 DM during the period of the years 1980—1990 (retrospective investigation) and in the period of the years 2012—2022 (prospective study).&#x0D; Materials and methods. The study was conducted on the basis of the Department of Endocrinology of the SI «Institute of Child and Adolescent Health of the NAMS of Ukraine». Examinations involved 605 pediatric patients: 285 patients (126 children and 159 adolescents) in the retrospective study, and 320 subjects (186 children and 134 adolescents) in the group of prospective study. All patients underwent somatic, neurological, and clinical examinations.&#x0D; Results and discussion. It haі been determined that in children and adolescents with type 1 diabetes mellitus, PVI clinical manifestations were present in all physiological body systems and often occur under the mask of various somatic diseases. The most typical PVI clinical syndromes in pediatric patients with DM included orthostatic hypotension, tachycardia at rest, hypohidrosis, gastroparesis, constipation, and urinary incontinence. The incidence of PVI syndromes in the groups of patients in the prospective study (years 2012-2022) was lower than in the retrospective study (years 1980—1990) owing to the use of the novel technologies for the DM treatment.&#x0D; Conclusions. The labile, severe course of type 1 diabetes mellitus in children often triggers the development of autonomic disorders, which are predictors and manifestations of neurological disorders. As the overall duration of the disease increases and carbohydrate metabolism is not compensated properly, the number of functional organic neurological complications increases. Damage to immature brain structures affects their further development and forms the basis for the long-term neurological complications in older age.

Objective:The incidence of type 1 diabetes mellitus in children is highly variable in the world. The aim of our study was to: 1) analyze the evolution of the incidence of childhood type 1 diabetes in Romania between 1996 and 2015, and: 2) to search for differences amongst age groups, gender, geographic regions and month of diagnosis.Methods:Data on all new cases of type 1 diabetes, aged <15 years, obtained from two independent sources, were included in the study. The statistical methods included modeling of the incidence rates, adjusting for age, sex, calendar year, geographic region and seasonality.Results:The study group was composed of 5422 children, with overall completeness of ascertainment estimated at 93.7%. The incidence rate (per 100.000 person-years) rose continuously, from 4.7 [95% confidence interval (CI) 3.9-5.7] in 1996 to 11.0 (95% CI 9.9-12.2) in 2015, by a yearly rate of 5.1%, highest in the youngest and lowest in the oldest children. The mean incidence was significantly higher (p<0.0001) in Transylvania (7.9, 95% CI 7.6-8.3) than in Moldavia (6.5, 95% CI 6.2-6.9) and Muntenia (7.0, 95% CI 6.7-7.3), probably due to differences regarding ethnicity and lifestyle. The monthly incidence showed a sinusoidal pattern, peaking in January and being minimum in June.Conclusion:The incidence of type 1 diabetes mellitus in Romanian children increased continuously during the study period by a rate that, if maintained, would lead to its doubling every 14 years. Important differences were established between geographic regions and seasonality at diagnosis.