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Risk of Complications in Youth-Onset Type 2 Diabetes

More aggressive screening and treatment is needed in children with type 2 diabetes to prevent complications as they get older. With the increase in children with type 2 diabetes, possibly as a consequence of the rise in childhood obesity, the prevalence of diabetes-related complications in this population clearly warrants further investigation.

To compare the prevalence of diabetes-related complications in youth-onset T2DM with their prevalence in type 1 diabetes mellitus (T1DM), a clinic-based, comparative study of patients aged <18 years with T1DM or T2DM, who attended a single diabetes complications assessment center in Australia between 1996 and 2005. Assessment of diabetes-related complications was made at each 2 h visit.

Outcome measures Microalbuminuria were defined as an albumin excretion rate 20 mg/min in at least two of three overnight urine collections or an albumin to creatinine ratio 2.5 mg/mmol. Glycemic control was assessed by measurement of glycated hemoglobin (HbA1c) levels; the nondiabetic range was 4–6%. Dyslipidemia was defined as a total cholesterol level >5.2 mmol/l and a triglyceride level >1.7 mmol/l. Autonomic neuropathy, retinopathy, thyroid function, and hypertension were also evaluated.
The study enrolled 1,433 patients with T1DM and 68 patients with T2DM. Patients with T1DM were predominantly white, whereas those with T2DM had more variation in their ethnic background. The patients with T1DM had a median of 2 complications assessments each (range 1–12). Of the patients with T2DM, 36 underwent complications assessment (median 2 assessments per patient, range 1–4), 25 had gradable retinopathy tests, 24 had peripheral-nerve testing, 23 had autonomic-nerve testing, and all underwent measurement of albumin excretion rate.

Patients with T2DM who attended complications assessments were more likely to come from an urban than a rural area (91% vs 9%); however, there were no differences in socioeconomic disadvantage scores, age or HbA1c levels between attendees and nonattendees. Patients with T1DM had a longer duration of diabetes (6.8 vs 1.3 years) and higher median HbA1c level (8.5% vs 7.3%) than patients with T2DM. Although there was no difference in the proportion of overweight patients in the two groups, patients with T2DM were more likely to be obese. Retinopathy was more common in T1DM than in T2DM patients (20% vs 4%), whereas T2DM was more strongly associated than T1DM with microalbuminuria (28% vs 6%) and hypertension (36% vs 16%). Patients with T2DM were also more likely to have dyslipidemia than patients with T1DM. Rates of neuropathy were similar in both groups. In a multivariate analysis, high HbA1c was a strong predictor of microalbuminuria in T2DM (odds ratio [OR] 1.67). By contrast, older age (OR 1.3) and systolic hypertension (OR 3.63) were associated with microalbuminuria in T1DM.

From the results it was concluded that despite greater glycemic control and shorter duration of disease, adolescents with T2DM had a higher prevalence of microalbuminuria and hypertension than their counterparts with T1DM.

Physicians have long known that insulin resistance (and possibly hyperglycemia) can be present for some time before an individual is diagnosed with T2DM, leading to the presence of diabetes complications at the time of adult diagnosis. T2DM is also characterized by high levels of inflammatory adipokines and low levels of adiponectin, which are associated with microvascular and macrovascular disease.1 As the prevalence of youth-onset T2DM has increased, it is likely that diabetes complications will frequently be detected when affected individuals are still fairly young.

The study by Eppens et al. demonstrates that adolescents with T2DM do indeed have a high incidence of the diabetes-related complications—microalbuminuria, hypertension, and dyslipidemia—early in the course of their disease. This information is particularly alarming, given the study in Pima Indians,2 which showed that the death rate from end-stage renal disease was twice as high in individuals diagnosed with T2DM in adolescence, compared with the rate in individuals diagnosed later in life—and the death rate from all causes was three times higher in individuals with youth-onset T2DM than in the nondiabetic population.2
In the study of Eppens et al., hypertension and microalbuminuria occurred more frequently in adolescents with T2DM than in adolescents with T1DM. This difference occurred despite the mean HbA1c level of 7.3% for youth-onset T2DM being 1.3% lower than the mean HbA1c level of adolescents with T1DM, and despite a shorter duration of diabetes in the T2DM than in the T1DM cohort (1.3 vs 6.8 years). Furthermore, dyslipidemia was detected in more than half of patients with youth-onset T2DM. This finding suggests that hypertension, microalbuminuria, and diabetes might all be manifestations of the metabolic syndrome that occur coincidently with (rather than as a result of) hyperglycemia. Many of the individuals with youth-onset T2DM were only screened once for the presence of diabetes-related complications, which suggest these complications could actually be more common than was documented by the authors. This study clearly highlights the need for physicians to monitor for complications early in the course of youth-onset T2DM and to treat elevated blood pressure, dyslipidemia, microalbuminuria, and hyperglycemia intensively in these patients.3 Nevertheless, several studies have indicated that practitioners often fail to achieve target HbA1c levels in adolescent patients with T2DM. Intensive multidisciplinary therapy similar to that undertaken in the Diabetes Control and Complications Trial (DCCT) for individuals with T1DM should, therefore, be implemented for adolescents with T2DM.4

The findings of Eppens et al. have enormous clinical implications. A multicenter study found that at diabetes centers throughout the US, 12–17% of individuals with T2DM had not been screened for the presence of diabetes-related complications.5 These data suggest that practitioners need to be made aware of the high prevalence of cardiovascular risk factors in adolescents with T2DM and to be rigorous in screening all patients at the time of diagnosis.

References
1. Weiss R and Caprio S (2006) Altered glucose metabolism in obese youth. Pediatr Endocrinol Rev 3: 233–238 | PubMed |
2. Pavkov ME et al. (2006) Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. JAMA 296: 421–426 | Article | PubMed | ChemPort |
3. American Diabetes Association (2005) Standards of medical care in diabetes. Diabetes Care 28 (Suppl): S4–S36
4. Minutolo R et al. (2006) Management of cardiovascular risk factors in advanced type 2 diabetic nephropathy: a comparative analysis in nephrology, diabetology and primary care settings. J Hypertens 24: 1655–1661 | PubMed | ChemPort |
5. Davis V et al. (online 24 June 2006) Pediatric type 2 diabetes: current evaluation and treatment pattern in the U S [abstract]. [http://www.abstracts2view.com/endo/view.php?nu=ENDO06L_P1-598] (accessed 19 October 2006)
Neurology, December 2006.

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