Timing Is Everything: Age of Onset Influences Long-Term Retinopathy Risk in Type 2 Diabetes, Independent of Traditional Risk Factors

Wong, Jencia; Molyneaux, Lynda; Constantino, Maria; Twigg, Stephen M.; Yue, Dennis K.

doi:10.2337/dc08-0580

Cited by 123 publications

(111 citation statements)

References 20 publications

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RESEARCH DESIGN AND METHODS

Complication status was assessed according to a standard protocol and extracted from our electronic database.

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mentioning

confidence: 99%

“…In the first part, prospectively collected clinical complications data from 354 patients with young-onset type 2 diabetes diagnosed between the ages of 15 and 30 years (T2DM [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] ) were compared with 1,062 subjects with type 2 diabetes onset between the ages of 40 and 50 years (T2DM 40-50 ), after matching for duration of known diabetes. Groups with older age were not used for direct comparison to minimize the additional confounding effect of chronological age on macrovascular complications.…”

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confidence: 99%

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An Inverse Relationship Between Age of Type 2 Diabetes Onset and Complication Risk and Mortality: The Impact of Youth-Onset Type 2 Diabetes

et al. 2016

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OBJECTIVEThis study compared the prevalence of complications in 354 patients with T2DM diagnosed between 15 and 30 years of age (T2DM [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] ) with that in a durationmatched cohort of 1,062 patients diagnosed between 40 and 50 years (T2DM [40][41][42][43][44][45][46][47][48][49][50] ). It also examined standardized mortality ratios (SMRs) according to diabetes age of onset in 15,238 patients covering a wider age-of-onset range. RESEARCH DESIGN AND METHODSComplication status was assessed according to a standard protocol and extracted from our electronic database. Survival status was ascertained by data linkage with the Australian National Death Index. SMRs were calculated in comparison with the background Australian population and analyzed according to age of onset. RESULTSAfter matching for duration, despite their younger age, T2DM 15-30 had more severe albuminuria (P = 0.004) and neuropathy scores (P = 0.003). T2DM 15-30 were as commonly affected by metabolic syndrome factors as T2DM 40-50 but less frequently treated for hypertension and dyslipidemia (P < 0.0001). An inverse relationship between age of diabetes onset and SMR was seen, which was the highest for T2DM 15-30 (3.4 [95% CI 2.7-4.2]). SMR plots adjusting for duration show that for those with T2DM 15-30 , SMR is the highest at any chronological age, with a peak SMR of more than 6 in early midlife. In contrast, mortality for older-onset groups approximates that of the background population. CONCLUSIONSThe negative effect of diabetes on morbidity and mortality is greatest for those diagnosed at a young age compared with T2DM of usual onset. These results highlight the growing imperative to direct attention toward young-onset T2DM and for effective interventions to be applied before middle age.Type 2 diabetes is well recognized to be a heterogeneous disorder, and its effect on morbidity and mortality may not be identical within this diagnosis. No longer just a disorder of mature age, there is now a well-recognized trend toward younger people presenting with this disease, particularly for some ethnic groups. Adolescents accounted for less than 4% of incident type 2 diabetes cases in the U.S. 15 years ago, but in a more

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“…

RESEARCH DESIGN AND METHODS

Complication status was assessed according to a standard protocol and extracted from our electronic database.

…”

mentioning

confidence: 99%

mentioning

confidence: 99%

An Inverse Relationship Between Age of Type 2 Diabetes Onset and Complication Risk and Mortality: The Impact of Youth-Onset Type 2 Diabetes

et al. 2016

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“…This form of diabetes appears to be phenotypically more aggressive, with poorer metabolic control at presentation and an inherent increased risk of retinopathy compared with later onset disease [1][2][3].…”

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confidence: 99%

Mitochondrial DNA content in peripheral blood monocytes: relationship with age of diabetes onsetand diabetic complications

et al. 2009

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Aims/hypothesis We examined whether age of type 2 diabetes onset is related to mitochondrial DNA content in peripheral blood monocytes (PBMCs). Methods PBMCs were isolated from 65 patients with type 2 diabetes. To minimise age as a confounder, only patients aged ≥50 years were studied. Sample mitochondrial DNA (mtDNA) content was determined by amplification of the mitochondrial gene CYT-B (also known as MT-CYB) and adjusted for single-copy nuclear control genes (36B4 [also known as RPLPO] and GAPDH). Results Age of diabetes onset ranged from 25 to 69 years. There was a significant positive relationship between age of diabetes onset in quartiles and mtDNA content for the whole group (p= 0.02 for trend). When stratified by the presence of diabetes complications, a strong positive relationship was observed between age of diagnosis and mtDNA content for participants without diabetic complications (r = 0.7; p = 0.0002), but not for those with complications (r=−0.04; p=0.8). Multivariate analysis confirmed age of onset and complication status as independent determinants. There was co-linearity between age of onset and disease duration, with similar relationships also seen between duration and mtDNA content. Conclusions/interpretation An earlier age of type 2 diabetes onset is associated with a lower PBMC mtDNA content, but only in patients without diabetes complications. This may reflect a differing biology of PBMC mtDNA in those with early-onset diabetes and those who are prone to complications. PBMC mtDNA depletion may accelerate diabetes onset; however the independent effect of diabetes duration remains to be evaluated.

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“…One hypothesis to explain these observations proposes that the longer disease duration and exposure to adverse risk factors for early-onset T2DM patients lead to diabetes-related complications, with significant morbidity and mortality. Another hypothesis suggests that early diagnosis of T2DM in young subjects identifies an inherently aggressive phenotype that develops more complications than lateonset disease 4,5 .…”

Section: Introductionmentioning

confidence: 99%

Association of adenosine triphosphate-binding cassette transporter A1 gene polymorphism with lipid profiles and early-onset type 2 diabetes

Lu¹,

Liao²,

Wang³

et al. 2014

ScienceAsia

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Adenosine triphosphate-binding cassette transporter A1 (ABCA1) plays an important role in lipid metabolism and is involved in diabetes. We investigated the associations between lipid profiles and an early-onset diabetic phenotype with ABCA1 genotypes among 999 type 2 diabetes mellitus patients in the Han Chinese population of Taiwan. During study enrolment, blood samples were collected by venipuncture from these patients for genomic DNA isolation and serological tests, and data related to the diabetes age of onset were collected using a self-report questionnaire. Four single-nucleotide polymorphisms (SNPs) were selected for genotyping by polymerase chain reaction in each patient. The present study found that the high-density lipoprotein (HDL) levels were significantly different among patients with different genotypes at SNP rs2487039 (p = 0.018). The body mass index (BMI) was also significantly different among patients with different genotypes at SNP rs2487039, rs2230806, and rs200069 (p = 0.009, 0.004, and 0.003, respectively). The polymorphisms at position rs10121901 in ABCA1 were statistically associated with development of early-onset type 2 diabetes mellitus (p = 0.013), with an odds ratio of 0.78 (95% confidence interval: 0.64-0.95). In conclusion, an ABCA1 variant is associated with HDL level, BMI, and early-onset type 2 diabetes mellitus in a specific Taiwanese population.

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Timing Is Everything: Age of Onset Influences Long-Term Retinopathy Risk in Type 2 Diabetes, Independent of Traditional Risk Factors

Cited by 123 publications

References 20 publications

An Inverse Relationship Between Age of Type 2 Diabetes Onset and Complication Risk and Mortality: The Impact of Youth-Onset Type 2 Diabetes

An Inverse Relationship Between Age of Type 2 Diabetes Onset and Complication Risk and Mortality: The Impact of Youth-Onset Type 2 Diabetes

Mitochondrial DNA content in peripheral blood monocytes: relationship with age of diabetes onsetand diabetic complications

Association of adenosine triphosphate-binding cassette transporter A1 gene polymorphism with lipid profiles and early-onset type 2 diabetes

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