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Develop Your Own Curriculum. There is a strong hereditary likely multigenic component to the disease, with the role of genetic determinants illustrated when differences in the prevalence of type 2 diabetes mellitus in various racial groups are considered[ 17 ]. Although substantial progress in our knowledge of the genetic basis of type 2 diabetes mellitus is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder[ 17 ].
Furthermore, the recent increases observed in diabetes mellitus prevalence are too quickly to be the result of increased gene frequency and altered gene pool, emphasizing the importance of environmental factors. It is well recognized that insulin resistance to insulin-stimulated glucose uptake is a characteristic finding in patients with type 2 diabetes mellitus and impaired glucose metabolism. The evolution from normal to impaired glucose tolerance IGT is associated with a worsening of insulin resistance.
Impaired glucose tolerance is an intermediate stage in the natural history of type 2 diabetes mellitus and is a predictor of the risk of developing diabetes mellitus and cardiovascular disease[ 7 , 10 , 11 , 18 ]. However, there is a high spontaneous conversion rate from IGT to normal glucose tolerance in the next 3 to 5 years in children and adolescents with impaired glucose tolerance[ 19 , 20 ].
This normalization has been attributed to changes of insulin resistance at end of puberty. Puberty appears to play a major role in the development of type 2 diabetes mellitus in children[ 11 ]. During puberty, there is increased resistance to the action of insulin, resulting in hyperinsulinemia. After puberty, basal and stimulated insulin responses decline.
Increased growth hormone secretion in puberty is discussed to be responsible for the insulin resistance during puberty[ 21 ].
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Given this information, it is not surprising that the peak age at presentation of type 2 diabetes mellitus in children coincides with the usual age of mid-puberty[ 3 , 11 ]. In patients with type 2 diabetes mellitus, impaired insulin action and insulin secretory failure are both present. It has been proposed that hyperglycemia may worsen both insulin resistance and insulin secretory abnormalities, thus enhancing the transition from impaired glucose tolerance to diabetes mellitus[ 11 ]. The adverse effect of obesity on glucose metabolism is evident early in childhood. Furthermore, the inverse relationship between insulin sensitivity and abdominal fat is stronger for visceral than for subcutaneous fat [ 22 , 23 ].
It is interesting to note that adipose tissue expanding in the obese state synthesizes and secretes metabolites and signaling proteins like leptin, adiponectin, and tumor necrosis factor-alpha. These factors are known to alter insulin secretion and sensitivity and even cause insulin resistance under experimental and clinical conditions[ 24 ]. Racial differences in insulin sensitivity are also evident in childhood. African-American 7- to year-old children have significantly higher insulin levels than age-matched white children[ 25 ].
These data suggest that particular ethnic groups may have a genetic predisposition to insulin resistance, which may increase their risk for type 2 diabetes mellitus. In concordance, obese Swedish children have higher fasting glucose levels than obese German children[ 26 ].
The prevalence of type 2 diabetes mellitus in children and adolescents in the United States is approximately Furthermore, the great majority of the children were obese. Screening studies in obese adolescents have reported a prevalence of 0. Within the whole pediatric cohort surveyed, the overall incidence of type 2 diabetes mellitus remained low when compared with type 1 diabetes mellitus.
Obesity is the hallmark of type 2 diabetes mellitus[ 10 ]. Most children with type 2 diabetes mellitus are obese or extremely obese at diagnosis and present with glucosuria without ketonuria, absent or mild polyuria and polydipsia, and little or no weight loss[ 3 , 10 ]. Currently, children with type 2 diabetes mellitus are usually diagnosed over the age of 10 years and are in middle to late puberty[ 3 , 10 , 11 ].
In the type 2 diabetes mellitus mildest form, the diagnosis is made in an asymptomatic child during a routine medical check-up by detection of hyperglycaemia or glycosuria[ 10 ]. One third of patients are diagnosed by urinanalysis during routine physical examination[ 10 , 11 ]. In its severest form, the child presents with polyuria, polydipsia, and weight loss. Vary rare, type 2 diabetes mellitus manifest with a hyperglycaemic hyperosmolare coma. With these clinical pictures, often the distinction from type 1 diabetes mellitus is not possible until months later, when insulin requirements decline and a non-insulin-dependent course develops without dependence on insulin for survival.
Comparison between Caucasian and non-Caucasian children and adolescents with type 2 diabetes mellitus.
Children with type 2 diabetes mellitus frequently have a family history of type 2 diabetes mellitus and those of non-European ancestry Americans of African, Hispanic, Asian, and American Indian descent are disproportionately represented. Of note, diabetes mellitus in parents or other relatives may not be recognized until the child is diagnosed. Acanthosis nigricans and polycystic ovarian syndrome PCOS , disorders associated with insulin resistance and obesity, are common in youth with type 2 diabetes mellitus[ 10 ].
Acanthosis is a cutaneous finding characterised by velvety hyperpigmented patches most prominent in intertrigenous area. It is recognised more frequently in darker-skinned obese individuals. PCOS is characterised by hyperandrogenism and chronic anovulation. Lipid disorders and hypertension also occur more frequently in children with type 2 diabetes mellitus.
The minority populations demonstrated at manifestation of diabetes mellitus frequently more symptoms and higher insulin and C-peptide levels[ 11 ]. They all are associated with mental retardation and frequently to extreme obesity. Individuals with type 2 diabetes mellitus may have clinical presentations indistinguishable from those of patients with other types of diabetes mellitus[ 10 ].
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This is relevant because as the number of children with type 2 diabetes mellitus increases, it becomes increasingly important to classify their diabetes mellitus correctly so that appropriate therapy may be instituted. They have a short duration of symptoms and frequently have ketoacidosis at presentation[ 7 , 10 , 35 ]. After metabolic stabilization, they may have an initial period of diminished insulin requirement, after which they require insulin for survival. For example, the increased prevalence of type 2 diabetes mellitus within the whole population means that many individuals with type 1 diabetes mellitus are now more likely to have a family history of type 2 diabetes mellitus.
Double diabetes mellitus or type 1. The accelerator hypothesis postulates a shared basis for both type 1 and type 2 diabetes mellitus: Obesity and puberty are important factors for developing insulin resistance in childhood and adolescence[ 22 ]. In conclusion, type 1 and type 2 diabetes mellitus do not seem to be completely distinctive and can overlap considerably.
Therefore, serology cannot completely distinguish these two types of diabetes mellitus. Patients with MODY have a dominant genetic trait, usually are non-obese and have low fasting insulin levels. Recent studies suggest that the clinical presentation of MODY is broad, ranging from asymptomatic hyperglycemia to a severe acute presentation.
These gene abnormalities are thought to be rare, and molecular diagnostic testing. In case of asymptomatic manifestation, fasting glucose, HbA1c, or oGTT test has to be repeated on another day for diagnosis[ 7 , 10 , 18 ]. In most patients with diabetes mellitus, classification can be made reliably on the basis of clinical presentation and course[ 7 , 10 , 18 ].
To achieve a high degree of sensitivity, a combination of test is required, which greatly increases the cost of classification. Flow sheet for classification of diabetes mellitus in children and adolescents. Adapted from Reference , cave autoantibodies also appear in type 2 diabetes mellitus. Maturity onset of diabetes mellitus in youth. C-peptide levels are elevated in individuals with type 2 diabetes mellitus in contrast to patients with type 1 diabetes mellitus or MODY diabetes.
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Most of the European Caucasian children and adolescents with type 2 diabetes mellitus and one third of the American children were asymptomatically at diagnosis. According to this, the prevalence in screening studies in Europe of obese children was much higher than the prevalence rate reported in the standardised documentation system of diabetes mellitus for example in Germany[ 32 , 46 ]. Therefore it is likely that, as with adults, undiagnosed type 2 diabetes mellitus is a common condition in childhood[ 47 ].
In conclusion, a screening of type 2 diabetes mellitus seems necessary since unrecognised hyperglycaemia would undoubtedly contribute to both microvascular and macrovascular risk in later life[ 11 ]. However, at the present time, a general screening for type 2 diabetes mellitus in youth is unlikely to be cost-effective. Therefore a targeted screening seems to be necessary. Consistent with the recommendations for screening in adults, only children at substantial risk for the presence or the development of type 2 diabetes mellitus should be tested.
Testing should be performed every 2 years starting at the age of 10 years or at onset of puberty if it occurs in a younger age by fasting glucose or oGTT[ 7 ]. However, these screening recommendations have some pitfalls. Requirements for testing an asymptomatic group include the availability of a test that is sensitive few false negatives and accurate with acceptable specificity minimal number of false positive. Since fasting blood glucose failed to diagnose diabetes mellitus in one fourth of children with type 2 diabetes mellitus in the European cohort[ 3 ], oGTT seems to be a better screening tool even if fasting glucose is preferred because of its lower costs and greater convenience.
However, the low reproducibility of an oGTT has to be kept in mind[ 48 ].
Type 2 Diabetes in Children and Adolescents | AMERICAN ACADEMY OF PEDIATRICS | Pediatrics
Using the criteria 1 type 2 diabetes mellitus in the first or second degree relatives, 2 onset of puberty, and 3 extreme obesity allows to identify the great majority of overweight European children, which should be screened by oGTT, when two of this three criteria are fulfilled[ 49 ]. Studies using HbA1c as screening tool were disappointing, since one third of the asymptomatic children with type 2 diabetes mellitus demonstrated normal values[ 3 ]. The standardisation process of the HbA1c may have improved its screening value, since HbA1c has been included in the ADA recommendation for the diagnosis of diabetes mellitus[ 18 , 45 ].
However, studies testing the usefulness of HbA1c after the standardisation process as screening tool are missing yet. The chronic complications of diabetes mellitus in adults include macrovascular disease like accelerated development of cardiovascular disease leading to stroke and myocardial infarction, and microvascular diseases like retinopathy, nephropathy and neuropathy leading to end-stage renal disease, loss of visual acuity, and limb amputations. Therefore, children and adolescents with type 2 diabetes mellitus have a higher risk for complication as compared to adults with diabetes mellitus.
Accordingly, developing type 2 diabetes mellitus at a younger age is also associated with a much higher risk of long-term cardiovascular disease than those who develop type 2 diabetes mellitus in middle age[ 51 ]. Young people with type 2 diabetes mellitus appear to be at a much higher risk of developing early diabetes mellitus associated complications than those with type 1 diabetes mellitus. This higher level of risk does not appear to be related to overall levels of glycemic control or duration of disease but to occurrence of hypertension and dyslipidemia[ 52 ]. These cardiovascular risk factors are more frequent in adolescents suffering from type 2 diabetes mellitus compared to type 1 diabetes mellitus[ 35 ].
These prevalences are similar to cardiovascular risk factors in European adolescents with type 2 diabetes mellitus[ 4 , 53 ]. We know little about the onset and progress of macrovascular disease in children and adolescents with type 2 diabetes mellitus. Arteriosclerosis is a time dependent phenomenon, and thus the absolute time from diagnosis to developing pathological cardiovascular lesions may be many years - in that sense these children may be protected by age since they do not have pre-existing age related cardiovascular disease.
However, already adolescents with type 2 diabetes mellitus demonstrated an increased intima-media thickness[ 54 ], which is predictive for heart attack and stroke[ 55 ]. Microvascular disease is the hallmark of hyperglycaemia diagnosed at a young age.
Type 2 diabetes mellitus in children and adolescents
Data from Japanese, Pima Indian children show the presence of microvascular diabetic complications already at diagnosis and follow-up[ 1 ]. The American Academy of Pediatrics has, very recently, published management guidelines how to treat children and adolescents with type 2 diabetes mellitus[ 9 ]. The ideal goal of treatment is normalization of blood glucose values and HbA1c[ 10 ].
Successful control of the associated comorbidities, such as hypertension and dyslipidemia, is also important[ 10 ]. The ultimate goal of treatment is to decrease the risk of acute and chronic complications associated with diabetes mellitus. Most of the recommended guidelines for treatment in children with type 2 diabetes mellitus are extrapolated from experience gained in adults[ 7 , 9 , 10 ].
Despite of severe manifestation, initial management of obese children and adolescents with type 2 diabetes mellitus should consist of behaviour modification strategies for lifestyle change such as decreasing high-caloric high-fat food choice and sedentary behaviour, while increasing physical activity[ 58 ].
Weight control is essential for reaching treatment goals and are effective to treat type 2 diabetes mellitus in adolescents[ 59 ]. However, lifestyle changes cannot be imposed and self-motivation is necessary[ 60 , 61 ]. Referral to a dietician with knowledge and experience in nutritional management of children with diabetes mellitus is necessary[ 60 ].
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