Young-onset type 2 diabetes and younger current age: increased susceptibility to retinopathy in contrast to other complications.

BACKGROUND: Type 2 diabetes diagnosed during youth and early adulthood is aggressive and associated with a high burden of vascular complications. The increase in complications is often attributed to long disease duration and poor metabolic control. Whether people with young-onset type 2 diabetes are inherently more susceptible to long-term complications than those diagnosed in later adulthood is unclear. METHODS: Prospective data from 3322 individuals, diagnosed between the age of 15 and 70 years and collected 10-25 years after diabetes diagnosis, were analysed. The cross-sectional associations between age at diagnosis and microvascular and macrovascular complications were analysed using logistic regression models, adjusted for duration of diabetes exposure and metabolic risk factors including blood pressure, cholesterol and updated mean HbA1c . RESULTS: The prevalence of retinopathy was highest in those with young-onset type 2 diabetes (diagnosed at age 15 to <40 years). After 10-15 years' diabetes duration, the adjusted odds ratio for retinopathy in this population was 2.8 (95% CI 1.9-4.1; reference group those diagnosed at 60 to <70 years of age). The odds of retinopathy remained higher in people with young-onset type 2 diabetes after longer durations of diabetes exposure; the odds decreased with increasing age at diagnosis. This pattern was not observed in models of other complications: after 10-15 years' diabetes exposure, the adjusted odds ratios for albuminuria, peripheral neuropathy and macrovascular disease in people with young-onset type 2 diabetes were 0.5 (95% CI 0.4-0.8), 0.7 (95% CI 0.5-1.1) and 0.2 (95% CI 0.1-0.3), respectively. CONCLUSION: After accounting for disease duration and other important confounders, people with type 2 diabetes diagnosed in youth and early adulthood (or with a younger current age) appeared to be inherently more susceptible to retinopathy. For other complications, adjusted risk appears highest in the oldest age of diagnosis group. These data have screening and treatment target implications.

The long-term impact of ferritin level on treatment and complications of type 2 diabetes.

AIM: To investigate if high-serum ferritin has long-term impact on response to treatment and the development of diabetic complications in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We analysed the record of 90 consecutive type 2 diabetic subjects who had serum ferritin level determined soon after diagnosis of diabetes and who also had long-term follow-up data. RESULTS: Patients with higher serum ferritin level had slightly worse triglyceride, blood pressure and liver enzyme levels at the end of follow up. However, ferritin level had no impact on the initial or final requirements for diabetic medication and the development of diabetic complications. CONCLUSIONS: Although elevated serum ferritin is a marker of insulin resistance and chronic inflammation, it is not necessarily a bad prognostic indicator that should affect the clinician's approach to management.

Better glycaemic control and risk reduction of diabetic complications in Type 2 diabetes: comparison with the DCCT.

OBJECTIVE: To construct dose response curves relating the development of diabetic complications (retinopathy and microalbuminuria) to mean glycaemic exposure in a cohort of Type 2 patients followed over a period of several years. This allows a comparison with similar data on Type 1 subjects reported by the Diabetes Control and Complications Trial (DCCT) and provides a rational basis for deciding what levels of glycaemic control should be aimed for in advising individual patients and in setting guidelines for conducting health services. RESEARCH DESIGN AND METHODS: This was an analysis of data prospectively collected in our computerized data base for Type 2 patients who attended and were followed up at the Complications Assessment Service of our Diabetes Center. The initial development of retinopathy and microalbuminuria was analyzed with respect to the mean HbA1c during the follow up period. Statistical procedures identical to those employed in the DCCT were used to construct the dose response curve. RESULTS: A smooth relationship between the development of retinopathy with increasing hyperglycaemia was found. For every 10% decrease in HbA1c, there was a 24%) (confidence interval (CI): 16-32) reduction in relative risk, about 2/3 of that reported for insulin-dependent diabetes mellitus (IDDM) patients. The relationship between microalbuminuria and HbAc was more linear and less steep with a relative risk reduction of 9% (CI: -2-19%) for any 10% fall in HbA1c, about 1/3 of that reported for IDDM subjects. No threshold of HbA1c can be found for the relative risk of developing complications. However, more cases of complications are prevented by the same degree of improvement in glycaemic control at higher levels of HbA1c. CONCLUSIONS: The development of diabetic retinopathy in Type 2 subjects is also related to the magnitude of hyperglycaemia although the degree of dependence is less than that in Type 1. Glycaemic control has less influence on microalbuminuria in Type 2. In terms of relative risk, no threshold of 'safe HbA1c' can be found but in absolute terms more cases of diabetic complications can be prevented by improving the glycaemic control of the very hyperglycaemic patients.

The metabolic syndrome in type 2 diabetes: When does it matter?

AIMS: Young adults with type 2 diabetes (T2Dm) present the clinician with the problem of when to start therapies for the primary prevention of vascular disease and how to identify those at most vascular risk. We examine whether the metabolic syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this context. METHODS: Data were collected from 5928 subjects with T2Dm, and subjects were categorized as having MetS by World Health Organization criteria (body mass index criteria modified for Asians using >23 kg/m2). The prevalence of macrovascular disease was examined by MetS status and age. RESULTS: The overall MetS prevalence was 72.3%. MetS was associated with an increased prevalence of ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001), coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across all age groups. MetS subjects had an IHD prevalence equivalent to that seen in subjects who were one decade older without MetS. The most significant impact of MetS was for the age group of 40-49 years with much lesser impact seen with progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with no MetS at age 40-50 years, p < 0.05; falling progressively to OR = 1.5 at age >70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft (CABG) and PVD. There was a strong relationship between the number of MetS risk factors and IHD prevalence (r = 0.99, p = 0.0001). CONCLUSIONS: These data suggest that MetS is particularly useful in stratifying vascular risk in younger T2Dm patients and in those with a high number of MetS components. For patients with MetS, especially those with a full house of MetS risk factors, commencing risk-lowering interventions 10 years earlier than their MetS-free counterparts could be considered.

Why does ethnicity affect prevalence of gestational diabetes? The underwater volcano theory.

To study why gestational diabetes (GDM) is more common in some ethnic groups than others, we tested the hypothesis that GDM is more common in people who are temporally closer to developing non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). The prevalence of GDM and the mean age of affected women in each major ethnic group were determined. From our database of NIDDM 6052 patients, the mean age of onset in each ethnic gorup was calculated and the mean difference between age of developing GDM and age of developing NIDDM derived (NIDDM-GDM age gap). This age gap was used to adjust for the susceptibility to GDM of each group. The overall prevalence of GDM was 6.7% (CI 6.0%-7.4%). In Anglo-Celtic women it was 3.0% (CI 2.3%-3.7%). For the other ethnic groups the prevalence and odds ratio (OR) were: Chinese (15.0% CI 11.8%-18.2% OR 5.6), Vietnamese (9.6% CI 6.6%-12.5% OR 3.6), Indian (16.7% CI 9.8%-23.5% OR 6.4), Arabic (7.3% CI 4.6%-10.1% OR 2.5) and Aborigines (10.1% CI 3.8%-16.4% OR 3.7). The OR for susceptibility to GDM did not change after adjustment for BMI and maternal age and it correlated significantly with the NIDDM-GDM age gap (r = -0.85; p = 0.03). However, it fell substantially after adjustment for NIDDM-GDM age gap. For women of different ethnic origins there is a difference in the time gap between their pregnancies and the time at which they would on average be expected to develop diabetes. This difference may be an important factor underlying the higher prevalence of GDM in some ethnic populations.