Ted Wu

Long-Term Complications and Mortality in Young-Onset Diabetes: Type 2 diabetes is more hazardous and lethal than type 1 diabetes

OBJECTIVE To evaluate long-term clinical outcomes and survival in young-onset type 2 diabetes (T2DM) compared with type 1 diabetes (T1DM) with a similar age of onset. RESEARCH DESIGN AND METHODS Records from the Royal Prince Alfred Hospital Diabetes Clinical Database, established in 1986, were matched with the Australian National Death Index to establish mortality outcomes for all subjects until June 2011. Clinical and mortality outcomes in 354 patients with T2DM, age of onset between 15 and 30 years (T2DM15–30), were compared with T1DM in several ways but primarily with 470 patients with T1DM with a similar age of onset (T1DM15–30) to minimize the confounding effect of age on outcome. RESULTS For a median observation period of 21.4 (interquartile range 14–30.7) and 23.4 (15.7–32.4) years for the T2DM and T1DM cohorts, respectively, 71 of 824 patients (8.6%) died. A significant mortality excess was noted in T2DM15–30 (11 vs. 6.8%, P = 0.03), with an increased hazard for death (hazard ratio 2.0 [95% CI 1.2–3.2], P = 0.003). Death for T2DM15–30 occurred after a significantly shorter disease duration (26.9 [18.1–36.0] vs. 36.5 [24.4–45.4] years, P = 0.01) and at a relatively young age. There were more cardiovascular deaths in T2DM15–30 (50 vs. 30%, P < 0.05). Despite equivalent glycemic control and shorter disease duration, the prevalence of albuminuria and less favorable cardiovascular risk factors were greater in the T2DM15–30 cohort, even soon after diabetes onset. Neuropathy scores and macrovascular complications were also increased in T2DM15–30 (P < 0.0001). CONCLUSIONS Young-onset T2DM is the more lethal phenotype of diabetes and is associated with a greater mortality, more diabetes complications, and unfavorable cardiovascular disease risk factors when compared with T1DM.

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

OBJECTIVE This study compared the prevalence of complications in 354 patients with T2DM diagnosed between 15 and 30 years of age (T2DM15–30) with that in a duration-matched cohort of 1,062 patients diagnosed between 40 and 50 years (T2DM40–50). 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 METHODS Complication 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. RESULTS After matching for duration, despite their younger age, T2DM15–30 had more severe albuminuria (P = 0.004) and neuropathy scores (P = 0.003). T2DM15–30 were as commonly affected by metabolic syndrome factors as T2DM40–50 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 T2DM15–30 (3.4 [95% CI 2.7–4.2]). SMR plots adjusting for duration show that for those with T2DM15–30, 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. CONCLUSIONS The 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.

Lipohypertrophy: does it matter in daily life? A study using a continuous glucose monitoring system

Aims:  To use continuous glucose monitoring (CGMS) to compare glucose profiles in people with type 1 diabetes following injection of insulin into an area affected by lipohypertrophy vs. an area not affected by lipohypertrophy.

Practical Guidance on the Use of Premix Insulin Analogs in Initiating, Intensifying, or Switching Insulin Regimens in Type 2 Diabetes

IntroductionPremix insulin analogs are a well-established treatment for type 2 diabetes (T2D). However, there is a lack of simple, clear guidance on some aspects of their use. These include choosing a regimen for insulin initiation, recognizing when patients need intensification of therapy, and switching from basal–bolus to a premix insulin analog when appropriate.MethodsAn independent expert panel formulated recommendations on the use in T2D of the premix insulin analog formulations widely available in Australasia, based on the available evidence and their own experience.ResultsResults from trials in both initiation and intensification of insulin show that no single insulin or regimen is best on all endpoints, and that improved glycemic control can be expected regardless of which regimen is used. Thus, individual patient factors and preferences become more important. Guidance is presented to help the clinician choose between a premix insulin analog or basal analog for insulin initiation, and to intensify insulin therapy using premix insulin analogs. Recommendations are made on dosing, titration, the concomitant use of non-insulin glucose-lowering drugs, and other practical issues, and on the special case of switching from basal–bolus to premix insulin analog therapy.ConclusionThis guidance is intended to help both general and specialist practitioners make informed choices and provide optimal care for patients with T2D. It emphasizes the importance of taking into account individual patient factors and preferences so that the choice of insulin regimen is individualized to the patient in the same way that glycemic targets are now individualized.FundingNovo Nordisk Region IO A/S.

Cardiac Effects of Sulfonylurea-Related Hypoglycemia

OBJECTIVE To determine the effect of sulfonylurea-related hypoglycemia on cardiac repolarization and ectopy in the setting of well-controlled type 2 diabetes. RESEARCH DESIGN AND METHODS Thirty subjects with sulfonylurea-treated type 2 diabetes underwent 48 h of concurrent continuous glucose monitoring and ambulatory electrocardiography. Ventricular repolarization (QTc) and QT dynamicity were analyzed during periods of hypoglycemia (<3.5 mmol/L for >20 min) and compared with periods of euglycemia and hyperglycemia combined. Cardiac ectopy rates during hypoglycemia were compared with ectopy rates when blood glucose was 4–10 mmol/L. RESULTS Mean HbA1c was 6.9% (52 mmol/mol). Hypoglycemia was detected in 9 of 30 subjects (30%); episodes were typically nocturnal (67%) and asymptomatic (73%). Hypoglycemia-associated QTc prolongation was seen in five of nine subjects with a large variation in individual response. Higher QT dynamicity, a poor prognostic factor in cardiac disease, was seen in subjects who experienced hypoglycemia compared with subjects who did not (0.193 vs. 0.159 for the nocturnal period; P = 0.01). This finding persisted after the hypoglycemic event. The rates of ventricular and supraventricular ectopy demonstrated a nonsignificant trend toward an increase during hypoglycemia (median rate ratio 1.58 and 1.33, respectively). Similar, nonsignificant results were observed in a separate insulin-treated cohort. CONCLUSIONS Hypoglycemia, often unrecognized, is a frequent finding in well-controlled sulfonylurea-treated type 2 diabetes. It is associated with the novel finding of increased QT dynamicity and QTc prolongation in some individuals. Our findings suggest sulfonylurea-related hypoglycemia can have detrimental cardiovascular sequelae. Similar effects are also seen in the setting of insulin therapy.

An association of large-fibre peripheral nerve dysfunction with non-invasive measures of liver fibrosis secondary to non-alcoholic fatty liver disease in diabetes

AIM To examine for an association of elevated lower-limb vibration perception threshold (VPT) with NAFLD fibrosis. METHODS Two cohorts from a tertiary diabetes centre were studied - Cohort 1, n=456 with type 1 or 2 diabetes, and Cohort 2, n=106 with type 2 diabetes mellitus. All underwent a detailed assessment, including VPT measurement. Cohort 2 also had liver ultrasound and transient elastography (TE). NAFLD Fibrosis Score (NFS) was calculated for all with available data. Follow-up VPT measurements on participants in Cohort 1 to 2014 were also collected if available. RESULTS Adjusted risk of higher VPT category (≥25V but <50V, or ≥50V, c.f. < 25V) was greater for high-risk NFS in both cohorts (Cohort 1, OR 2.22 [95% CI 1.24-3.98, p=0.007] and Cohort 2, OR 4.51 [95% CI 1.08-18.87], p=0.039) and higher liver stiffness measurement (LSM) by TE in Cohort 2 (OR for each unit natural log increase in LSM of 2.42 (95% CI 1.13-5.19), p=0.023). In Cohort 1, in those with VPT<50V and complete data, those with higher NFS had greater odds of increasing VPT category after 2.2 (IQR 1.5-2.9) years. CONCLUSIONS Higher VPT associates with markers of liver fibrosis due to NAFLD in diabetes mellitus.

Age of diabetes diagnosis and diabetes duration associate with glycated haemoglobin

An earlier age of diagnosis (r=-0.28, p<0.0001) and longer duration of type 2 diabetes (r=0.26, p<0.0001) were each found to correlate with higher HbA1c level, on analysis of a diabetes centre database in people under regular shared care. When combined, these biological variables strongly associate with the current HbA1c level.

Ethnic specific differences in survival of patients with type 2 diabetes: Analysis of data collected from an Australian multi-ethnic cohort over a 25 year period

AIMS To examine the survival of patients with type 2 diabetes from 7 ethnic groups, living in the shared environment of an Australian city. METHODS Hazard ratio of death (HR) after diagnosis of diabetes was compared between Anglo-Celtic (n=5433), Indigenous Australian (n=439), Pacific Islander (n=354), Mediterranean (n=3138), Arabic (n=768), Indian (n=702) and Chinese (n=1632) patients who live in metropolitan Sydney. Mortality was ascertained by data-linkage with the Australian National Death Index. The modulating effects of glycaemic control, diabetes/vascular complications and risk factors, year of diabetes diagnosis and duration of diabetes on ethnic differences were analysed by Cox regression. Socio-economic status and competence in English were also examined. RESULTS There were significant differences in survival between the ethnic groups; the Indigenous Australians had the highest HR for death (2.3, 95% CI 1.7-3.0) and the Chinese the lowest (0.4, 95% CI 0.4-0.5). The survival of the Anglo-Celtics (HR 1) was surprisingly poorer than for Indian (0.6, 95% CI 0.5-0.8), Arab (0.7, 95% CI 0.6-0.8) and Mediterranean groups (0.8, 95% CI 0.7-0.9). Prevalence of smoking and albuminuria were strongly associated with HR. The better survival of Chinese and Arab and the worse survival of Indigenous Australians remained after adjustment of risk factors. Need for an interpreter was a favourable risk factor for survival. CONCLUSIONS Ethnicity is a significant determinant of survival in type 2 diabetes and this is substantially but not completely mediated by smoking and vascular risk factors. The favourable impact associated with less competence in English may represent a Healthy-migrant effect.

Dipeptidyl peptidase-4 inhibitors as a third-line oral antihyperglycaemic agent in patients with type 2 diabetes mellitus: the impact of ethnicity.

Aims. The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment. The response of Asian and non-Asian patients to this regimen was also examined. Methods. The medical and computerized records of 80 patients were examined. These patients had baseline HbA1c levels ranging from 7.0 to 12.5% and had a DPP-4 inhibitor add-on therapy for a minimum period of 12 weeks. The primary endpoint was the change in HbA1c level before and after DPP-4 inhibitor treatment. Results. During oral triple therapy, there was a reduction of HbA1c from 8.3% (7.7–8.9) to 7.2% (6.8–7.6) and 26 patients (32.5%) achieved an HbA1c <7%. Poor baseline glycaemic control, lower BMI, and younger age were associated with a better response, but duration of diabetes and gender did not affect outcome. The HbA1c reduction was not different between Asians and non-Asians group [−1.00% (0.6–1.3) vs −0.90% (0.4–1.6)]. Conclusions. DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea. The improvement in HbA1c was similar between Asian and non-Asian patients.

Data collection on retinopathy as a public health tool: The Hubble telescope equivalent of looking back in time

OBJECTIVE To test whether the rate of diabetic retinopathy development in a population calculated from the prevalence of retinopathy and duration of diabetes can be used to assess their prior glycemic control. RESEARCH DESIGN AND METHODS 9281 patients with type 2 diabetes (T2DM) were grouped by duration of diabetes and plotted against the % of retinopathy in each band. The slope was used to calculate retinopathy development/year (RD/y). We correlated the RD/y with updated HbA1c within groups of different ethnicity, age of diabetes onset, year of the eye examination, socio-economic status and fluency in English. RESULTS Differences in ethnicity, age of diabetes onset and year of the eye examination affect RD/y to a degree predictable from their respective updated HbA1c. No such relationship with updated HbA1c was evident when a factor has no apparent effect on RD/y. CONCLUSIONS This relationship between prevalence of retinopathy and duration of diabetes can be used to assess future retinopathy burden. Perhaps more intriguing, the camera can be reversed to allow an estimate of prior glycemic control of a population from its retinopathy prevalence. Health care organizations can use this method to project future needs and to assess adequacy of prior glycemic control.