Maria Constantino

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.

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 group 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.

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

OBJECTIVE—To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia. RESEARCH DESIGN AND METHODS—Retinopathy data from 624 patients with a type 2 diabetes duration of 20–30 years (group A) were analyzed by stratifying patients according to age of onset of diabetes and glycemic control. Retinopathy status was scored clinically as per a modified Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. To obviate possible bias due to a higher attrition from comorbidities in those with later-onset diabetes and retinopathy, 852 patients with type 2 diabetes of shorter duration (10–12 years, group B) were similarly studied. RESULTS—Prevalence and severity of retinopathy was significantly higher in the younger-onset, group A patients. When further stratified according to mean A1C, retinopathy risk remained increased in younger-onset patients. The greatest impact was seen in those with a mean A1C >9% (odds ratio [OR] for retinopathy 16.6, 7.5, and 2.7 for age of diagnosis <45, 45–55, and >55 years, respectively, P = 0.003). By logistic regression, earlier type 2 diabetes onset is associated with increased retinopathy risk, independent of traditional risk factors (OR of retinopathy 1.9, 1.1, and 1 for age of onset <45, 45–55, and >55 years, respectively). Similar results were found in group B patients. CONCLUSIONS— These data suggest an increased inherent susceptibility to diabetic retinopathy with earlier-onset type 2 diabetes. This further supports the importance of delaying development of diabetes and also implies a need for more stringent metabolic targets for younger individuals.

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.

Strong family history predicts a younger age of onset for subjects diagnosed with type 2 diabetes

Aims:  Age of onset of type 2 diabetes is becoming earlier and with it there is an increase in the development of chronic complications. This study examined the relationship between the strength of family history of diabetes on (i) age of diabetes onset and (ii) prevalence of diabetic complications.

Gestational Diabetes Mellitus in Early Pregnancy: Evidence for Poor Pregnancy Outcomes Despite Treatment.

OBJECTIVE Recent guidelines recommend testing at <24 weeks of gestation for maternal dysglycemia in “high-risk” women. Evidence to support the early identification and treatment of gestational diabetes mellitus (GDM) is, however, limited. We examined the prevalence, clinical characteristics, and pregnancy outcomes of high-risk women with GDM diagnosed at <24 weeks of gestation (early GDM) and those with pre-existing diabetes compared with GDM diagnosed at ≥24 weeks of gestation, in a large treated multiethnic cohort. RESEARCH DESIGN AND METHODS Outcomes from 4,873 women attending a university hospital antenatal diabetes clinic between 1991 and 2011 were examined. All were treated to standardized glycemic targets. Women were stratified as pre-existing diabetes (n = 65) or GDM diagnosed at <12 weeks of gestation (n = 68), at 12–23 weeks of gestation (n = 1,247), or at ≥24 weeks of gestation (n = 3,493). RESULTS Hypertensive disorders in pregnancy including pre-eclampsia, preterm delivery, cesarean section, and neonatal jaundice (all P < 0.001) were more prevalent in women with pre-existing diabetes and early GDM. Macrosomia (21.8% vs. 20.3%, P = 0.8), large for gestational age (39.6% vs. 32.8%, P = 0.4), and neonatal intensive care admission (38.5% vs. 39.7%, P = 0.9) in women in whom GDM was diagnosed at <12 weeks of gestation were comparable to rates seen in women with pre-existing diabetes. CONCLUSIONS Despite early testing and current best practice treatment, early GDM in high-risk women remains associated with poorer pregnancy outcomes. Outcomes for those in whom GDM was diagnosed at <12 weeks of gestation approximated those seen in pre-existing diabetes. These findings indicate the need for further studies to establish the efficacy of alternative management approaches to improve outcomes in these high-risk pregnancies.

Morbidity and mortality in young-onset type 2 diabetes in comparison to type 1 diabetes: where are we now?

Increasingly, we recognise that type 2 diabetes in youth is a disease with an aggressive time course and a significant complication risk. On the other hand, outcomes for youth with type 1 diabetes appear generally to be improving. With increasing numbers of both types of diabetes in youth, it is timely that a comparative perspective is offered to help clinicians prognosticate more appropriately. Contemporary comparative studies add a new perspective to a consistent story, that for youth-onset type 2 diabetes, the development and progression of cardio-renal complications are increased and the survival prognosis is significantly worse than for type 1 diabetes. Here, we review this mounting evidence, highlight the importance of metabolic syndrome factors in the excess risk and underscore that there remains a significant mortality gap for youth with either type of diabetes, to be addressed as a matter of urgency.

Medication Safety: an audit of medication discrepancies in transferring type 2 diabetes mellitus (T2DM) patients from Australian primary care to tertiary ambulatory care.

OBJECTIVE To identify, classify and determine the factors associated with medication discrepancies for type 2 diabetes mellitus (T2DM) patients, referred from primary care to a tertiary ambulatory clinic. DESIGN Retrospective audit of outpatient clinic records. SETTING Royal Prince Alfred Hospital (RPAH) Diabetes Ambulatory Care Centre. PARTICIPANTS 300 randomly selected adult T2DM patients who attended the Diabetes Centre between 01 January 2010 and 31 December 2011. MAIN OUTCOME MEASURES The rates and types of medication discrepancies were identified by comparing the structured nurse-patient interview (SNPI) with the primary care [General Practitioner (GP)] referral letter, where the SNPI was considered the best possible medication history. Discrepancies were identified as addition, omission, dose and insulin-type discrepancies. Each category was mutually exclusive. RESULTS Over 80% of referral letters contained at least one discrepancy with a median of two discrepancies per referral. Of a total of 744 discrepancies, the majority were omissions (58.9%). Insulins had the highest discrepancy rate. Factors independently associated with medication discrepancies were GP referral letter type, total number of medications and medication regimen type. CONCLUSIONS A high rate of medication discrepancies was found in GP referral letters for patients referred to this clinic. Automated GP referral letters and inaccurate GP records may have contributed to this, highlighting the need for routine medication reconciliation at transitions of care, to ensure prescribers have access to correct medication information to inform decision-making and ensure optimal patient outcomes.

Identifying Glucokinase Monogenic Diabetes in a Multiethnic Gestational Diabetes Mellitus Cohort: New Pregnancy Screening Criteria and Utility of HbA1c.

OBJECTIVE Glucokinase monogenic diabetes (GCK–maturity-onset diabetes of the young [MODY]) should be differentiated from gestational diabetes mellitus (GDM) because management differs. New pregnancy-specific screening criteria (NSC) have been proposed to identify women who warrant GCK genetic testing. We tested NSC and HbA1c in a multiethnic GDM cohort and examined projected referrals for GCK testing. RESEARCH DESIGN AND METHODS Using a GDM database, 63 of 776 women had a postpartum oral glucose tolerance test suggestive of GCK-MODY. Of these 63 women, 31 agreed to undergo GCK testing. NSC accuracy and HbA1c were examined. Projected referrals were calculated by applying the NSC to a larger GDM database (n = 4,415). RESULTS Four of 31 women were confirmed as having GCK-MODY (prevalence ∼0.5–1/100 with GDM). The NSC identified all Anglo-Celtic women but did not identify one Indian woman. The NSC will refer 6.1% of GDM cases for GCK testing, with more Asian/Indian women referred despite lower disease prevalence. Antepartum HbA1c was not higher in those with GCK-MODY. CONCLUSIONS The NSC performed well in Anglo-Celtic women. Ethnic-specific criteria should be explored.

Suboptimal Performance of Blood Glucose Meters in an Antenatal Diabetes Clinic

OBJECTIVE The objective of this study was to evaluate the performance of blood glucose meters in diabetes associated with pregnancy (DP). RESEARCH DESIGN AND METHODS Finger-prick blood glucose levels measured using six different glucose meters on 102 patients with DP attending an antenatal clinic were compared with laboratory plasma glucose results. HbA1c and hematocrit were also measured. RESULTS The plasma glucose range was 2.2–9.4 mmol/L with hematocrit 33–37% and mean HbA1c 5.5% ± 0.56 (SD). All meters provided plasma equivalent results except one, which reported whole blood glucose that was adjusted to plasma equivalent values. The absolute glucose difference [meter − plasma glucose] was 0.232 ± 0.69 to 0.725 ± 0.62 mmol/L mean ± SD and bias ranged from 6.1 to 15.8%. Two meters were affected by hematocrit <36% (P < 0.05). CONCLUSIONS Blood glucose meters in current use are not optimally accurate when compared with plasma glucose measurement in DP. Recognition of this deviation is essential to prevent inappropriate treatment of DP.