Elizabeth Sellers

Type 2 Diabetes, Medication-Induced Diabetes, and Monogenic Diabetes in Canadian Children: A Prospective National Surveillance Study

OBJECTIVE To determine in Canadian children aged <18 years the 1) incidence of type 2 diabetes, medication-induced diabetes, and monogenic diabetes; 2) clinical features of type 2 diabetes; and 3) coexisting morbidity associated with type 2 diabetes at diagnosis. RESEARCH DESIGN AND METHODS This Canadian prospective national surveillance study involved a network of pediatricians, pediatric endocrinologists, family physicians, and adult endocrinologists. Incidence rates were calculated using Canadian Census population data. Descriptive statistics were used to illustrate demographic and clinical features. RESULTS From a population of 7.3 million children, 345 cases of non–type 1 diabetes were reported. The observed minimum incidence rates of type 2, medication-induced, and monogenic diabetes were 1.54, 0.4, and 0.2 cases per 100,000 children aged <18 years per year, respectively. On average, children with type 2 diabetes were aged 13.7 years and 8% (19 of 227) presented before 10 years. Ethnic minorities were overrepresented, but 25% (57 of 227) of children with type 2 diabetes were Caucasian. Of children with type 2 diabetes, 95% (206 of 216) were obese and 37% (43 of 115) had at least one comorbidity at diagnosis. CONCLUSIONS This is the first prospective national surveillance study in Canada to report the incidence of type 2 diabetes in children and also the first in the world to report the incidence of medication-induced and monogenic diabetes. Rates of type 2 diabetes were higher than expected with important regional variation. These results support recommendations that screening for comorbidity should occur at diagnosis of type 2 diabetes.

Earlier onset of complications in youth with type 2 diabetes

OBJECTIVE To evaluate the risk of complications in youth with type 2 diabetes. RESEARCH DESIGN AND METHODS Population-based cohorts of 342 youth (1–18 years of age) with prevalent type 2 diabetes, 1,011 youth with type 1 diabetes, and 1,710 nondiabetic control youth were identified between 1986 and 2007 from a clinical registry and linked to health care records to assess long-term outcomes using ICD-9CM and ICD-10CA codes. RESULTS Youth with type 2 diabetes had an increased risk of any complication (hazard ratio 1.47 [95% CI 1.02–2.12]). Significant adverse clinical factors included age at diagnosis (1.08 [1.02–2.12]), HbA1c (1.06 [1.01–1.12]), and, surprisingly, renin-angiotensin-aldosterone system (RAAS) inhibitor use (1.75 [1.27–2.41]). HNF-1α G319S polymorphism was protective in the type 2 diabetes cohort (0.58 [0.34–0.99]). Kaplan-Meier statistics revealed an earlier diagnosis of renal and neurologic complications in the type 2 diabetes cohort, manifesting within 5 years of diagnosis. No difference in retinopathy was seen. Cardiovascular and cerebrovascular diseases were rare; however, major complications (dialysis, blindness, or amputation) started to manifest 10 years after diagnosis in the type 2 diabetes cohort. Youth with type 2 diabetes had higher rates of all outcomes than nondiabetic control youth and an overall 6.15-fold increased risk of any vascular disease. CONCLUSIONS Youth with type 2 diabetes exhibit complications sooner than youth with type 1 diabetes. Younger age at diagnosis is potentially protective, and glycemic control is an important modifiable risk factor. The unexpected adverse association between RAAS inhibitor use and outcome is likely a confounder by indication; however, further evaluation in young people is warranted.

High Burden of Kidney Disease in Youth-Onset Type 2 Diabetes

OBJECTIVE To evaluate renal outcomes and survival in youth with type 2 diabetes (T2DM) versus type 1 diabetes (T1DM) versus nondiabetic control subjects. RESEARCH DESIGN AND METHODS In total, 342 prevalent youth (aged 1–18 years) with T2DM, 1,011 youth with T1DM, and 1,710 control subjects identified from 1986 to 2007 were anonymously linked to health care records housed at the Manitoba Centre for Health Policy to assess long-term outcomes using ICD codes. RESULTS Youth with T2DM were found to have a fourfold increased risk of renal failure versus youth with T1DM. Risk factors associated with renal failure were renin angiotensin aldosterone system inhibitor use and albuminuria in adolescence. Compared with control subjects (age, sex, and postal code matched), youth with T2DM had a 23-fold increased risk of renal failure and a 39-fold increased risk of dialysis. Kaplan-Meier survival at 10 years was 91.4% in the type 2 diabetic group versus 99.5% in the type 1 diabetic group (P < 0.0001). Renal survival was 100% at 10 years in both groups. It decreased to 92.0% at 15 years and 55.0% at 20 years in the type 2 diabetic group but remained stable in the type 1 diabetic group (P < 0.0001). CONCLUSIONS Youth with T2DM are at high risk of adverse renal outcomes and death. Albuminuria and angiotensin aldosterone system inhibitor use, which may be a marker of severity of disease, are associated with poor outcomes in early adulthood.

Physical activity for the prevention and management of youth-onset type 2 diabetes mellitus: focus on cardiovascular complications

With the growing prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) in youth, the challenge of cardiovascular disease risk management has entered the paediatric realm, affecting specialists, family physicians and allied healthcare professionals alike. Currently, there is little evidence to support optimal strategies for management of T2DM in youth and the associated cardiovascular complications. Physical activity plays a powerful role in the prevention and management of T2DM and cardiovascular disease in adults. This review will focus on the role of physical activity for the prevention of T2DM in youth and its associated cardiovascular complications. The first part describes the prevalence of cardiovascular risk factors in this cohort. The second part focuses on the role of physical activity in the prevention and management of T2DM in youth. Collectively, the limited intervention and observation studies published to date suggest that daily targets of 60–90 minutes of physical activity and less than 60 minutes of screen time (i.e. time spent in front of a television, computer or video games) are required for the prevention and management of T2DM in youth. Large-scale intervention studies are needed to determine the most effective physical activity strategies for the prevention and management of T2DM in youth.

Youth-Onset Type 2 Diabetes Consensus Report: Current Status, Challenges, and Priorities

Type 2 diabetes is a significant and increasing burden in adolescents and young adults. Clear strategies for research, prevention, and treatment of the disease in these vulnerable patients are needed. Evidence suggests that type 2 diabetes in children is different not only from type 1 but also from type 2 diabetes in adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as well as the risk of complications and the psychosocial impact, will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate both current and future research, treatment, and prevention approaches. This Consensus Report characterizes type 2 diabetes in children, evaluates the fundamental differences between childhood and adult disease, describes the current therapeutic options, and discusses challenges to and approaches for developing new treatments.

Large waist but low body mass index: the metabolic syndrome in Australian Aboriginal children.

OBJECTIVE To describe the prevalence and clinical characteristics of the metabolic syndrome (MetS) in a cohort of Australian Aboriginal children. STUDY DESIGN Body mass index (BMI), waist circumference, skin fold thickness, body fat percentage, insulin resistance, and the prevalence of MetS were evaluated in 486 children age 9 to 14 years from the Darwin Health Region, Northern Territory, Australia. RESULTS Using an age- and sex- specific definition, 14% of the children in the cohort had MetS, 6.4% were overweight, 4.9% were obese, and 26.2% had an elevated waist circumference. The mean percentage of body fat was 30.2%. The children with MetS had higher BMI and waist z-scores, percent body fat, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score, and skin fold thickness compared with those without MetS (P < .001); however, >50% of those with MetS were neither overweight nor obese. Waist circumference was significantly associated with insulin resistance as measured by the HOMA-IR (P < .001). CONCLUSIONS MetS is common in our cohort despite low rates of overweight and obesity. A tendency for central adiposity is already evident in these young children. Measurement of waist circumference may help identify Aboriginal children at high risk for MetS.

Metabolic Consequences of Hepatic Steatosis in Overweight and Obese Adolescents

OBJECTIVE To test the hypothesis that hepatic steatosis is associated with risk factors for type 2 diabetes in overweight and obese youth, mediated by cardiorespiratory fitness. RESEARCH DESIGN AND METHODS This was a cross-sectional study comparing insulin sensitivity between 30 overweight and obese adolescents with hepatic steatosis, 68 overweight and obese adolescents without hepatic steatosis, and 11 healthy weight adolescents without hepatic steatosis. Cardiorespiratory fitness was determined by a graded maximal exercise test on a cycle ergometer. Secondary outcomes included presence of metabolic syndrome and glucose response to a 75-g oral glucose challenge. RESULTS The presence of hepatic steatosis was associated with 55% lower insulin sensitivity (P = 0.02) and a twofold greater prevalence of metabolic syndrome (P = 0.001). Differences in insulin sensitivity (3.5 vs. 4.5 mU ⋅ kg−1 ⋅ min−1, P = 0.03), prevalence of metabolic syndrome (48 vs. 20%, P = 0.03), and glucose area under the curve (816 vs. 710, P = 0.04) remained between groups after matching for age, sex, and visceral fat. The association between hepatic steatosis and insulin sensitivity (β = −0.24, t = −2.29, P < 0.025), metabolic syndrome (β = −0.54, t = −5.8, P < 0.001), and glucose area under the curve (β = 0.33, t = 3.3, P < 0.001) was independent of visceral and whole-body adiposity. Cardiorespiratory fitness was not associated with hepatic steatosis, insulin sensitivity, or presence of metabolic syndrome. CONCLUSIONS Hepatic steatosis is associated with type 2 diabetes risk factors independent of cardiorespiratory fitness, whole-body adiposity, and visceral fat mass.

Dietary determinants of hepatic steatosis and visceral adiposity in overweight and obese youth at risk of type 2 diabetes

BACKGROUND Dietary determinants of hepatic steatosis, an important precursor for nonalcoholic fatty liver disease, are undefined. OBJECTIVE We explored the roles of sugar and fat intake as determinants of hepatic steatosis and visceral obesity in overweight adolescents at risk of type 2 diabetes. DESIGN This was a cross-sectional study of dietary patterns and adipose tissue distribution in 74 overweight adolescents (aged: 15.4 ± 1.8 y; body mass index z score: 2.2 ± 0.4). Main outcome measures were hepatic steatosis (≥5.5% fat:water) measured by magnetic resonance spectroscopy and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥0.25) measured by magnetic resonance imaging. Main exposure variables were dietary intake and habits assessed by the Harvard Youth Adolescent Food Frequency Questionnaire. RESULTS Hepatic steatosis and visceral obesity were evident in 43% and 44% of the sample, respectively. Fried food consumption was more common in adolescents with hepatic steatosis than in adolescents without hepatic steatosis (41% compared with 18%; P = 0.04). Total fat intake (β = 0.51, P = 0.03) and the consumption of >35% of daily energy intake from fat (OR: 11.8; 95% CI: 1.6, 86.6; P = 0.02) were both positively associated with hepatic steatosis. Available carbohydrate (β = 0.54, P = 0.02) and the frequent consumption of soda were positively associated with visceral obesity (OR: 6.4; 95% CI: 1.2, 34.0; P = 0.03). Daily fiber intake was associated with reduced odds of visceral obesity (OR: 0.82; 95% CI: 0.68, 0.98; P = 0.02) but not hepatic steatosis. CONCLUSION Hepatic steatosis is associated with a greater intake of fat and fried foods, whereas visceral obesity is associated with increased consumption of sugar and reduced consumption of fiber in overweight and obese adolescents at risk of type 2 diabetes.

Validation of a Pediatric Diabetes Case Definition Using Administrative Health Data in Manitoba, Canada

OBJECTIVE To validate a case definition for diabetes in the pediatric age-group using administrative health data. RESEARCH DESIGN AND METHODS Population-based administrative data from Manitoba, Canada for the years 2004–2006 were anonymously linked to a clinical registry to evaluate the validity of algorithms based on a combination of hospital claim, outpatient physician visit, and drug use data over 1–3 years in youth 1–18 years of age. Agreement between data sources, sensitivity, specificity, negative (NPV) and positive predictive value (PPV) were evaluated for each algorithm. In addition, ascertainment rate of each data source, prevalence, and differences between subtypes of diabetes were evaluated. RESULTS Agreement between data sources was very good. The diabetes definition including one or more hospitalizations or two or more outpatient claims over 2 years provided a sensitivity of 94.2%, specificity of 99.9%, PPV of 81.6% and NPV of 99.9%. The addition of one or more prescription claims to the same definition over 1 year provided similar results. Case ascertainment rates of both sources were very good to excellent and the ascertainment-corrected prevalence for youth-onset diabetes for the year 2006 was 2.4 per 1,000. It was not possible to distinguish between subtypes of diabetes within the administrative database; however, this limitation could be overcome with an anonymous linkage to the clinical registry. CONCLUSIONS Administrative data are a valid source for the determination of pediatric diabetes prevalence that can provide important information for health care planning and evaluation.

Altered plasma adipokines and markers of oxidative stress suggest increased risk of cardiovascular disease in First Nation youth with obesity or type 2 diabetes mellitus

Objective:  To evaluate cardiovascular disease risk in First Nation youth with and without type 2 diabetes mellitus (T2DM) or obesity by comparing pro‐ and anti‐inflammatory adipokines, markers of oxidative stress and the plasma phospholipid fatty acid profile.