Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease.

Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2-4 CKD, with and without diabetes, and healthy controls (n = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2-4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD.

Young adult onset type 2 diabetes versus type 1 diabetes: Progression to and survival on renal replacement therapy.

BACKGROUND: Young-onset type 2 diabetes is an aggressive disease characterized by development of diabetic complications, including nephropathy, early in the disease course. However, within the cohort of young-onset type 1 and type 2 diabetes there are limited comparative data regarding progression to ESKD requiring renal replacement therapy or renal-related death (RRT/RRD). METHODS: Probabilistic linkage of data from the RPAH Diabetes Centre, National Death Index and Australian and New Zealand Dialysis and Transplant Registry was undertaken. Cumulative Incidence Competing Risk and Cox Proportional Hazards Modelling approaches were utilized to examine progression to ESKD in young-onset type 1 and type 2 diabetes (age of diagnosis 15-35 years). FINDINGS: Unadjusted incidence rates (95% CI) of RRT/RRD in young-onset type 1 and type 2 diabetes were 3.1 (2.3-4.0) and 4.6 (3.7-5.7) per 1000 person years respectively. After adjustment for gender, ethnicity and duration of diabetes, the HR (95% CI) of RRT/RRD in young-onset type 2 diabetes was 2.0 (1.4-2.9). The HR remained higher after further adjustment for first available cholesterol, HbA1c and systolic blood pressure but not BMI. For those who progressed to RRT, prognosis was similar irrespective of diabetes type; cumulative incidence of mortality was 40% in both young-onset type 1 and type 2 diabetes after 6 years of dialysis. INTERPRETATION: Progression to RRT/RRD is greater in young-onset type 2 diabetes than in young-onset type 1 diabetes. The increased progression is associated with increased BMI. However, once ESKD is reached, individuals with young-onset type 1 and type 2 diabetes do equally poorly.

Secular Trends in Information Communications Technology: Access, Use, and Attitudes of Young and Older Patients With Diabetes.

BACKGROUND: Advances in information communications technology (ICT) provide opportunities for enhanced diabetes care. Knowledge of the more acceptable communication modalities in patients of different ages will help to inform the direction of future innovations. METHODS: An anonymous ICT survey (examining access and use of mobile phones, computers, tablets, and the Internet and attitudes toward e-mail, Web-based consultations, and online peer-support) was conducted at the Royal Prince Alfred Hospital Diabetes Centre in Sydney, Australia. Survey deployment occurred during 4-month periods in 2012 and 2017. Respondents were stratified by current age (<40 or ≥40 years). RESULTS: A total of 614 unselected patients (20% with type 1 diabetes, 55% with type 2 diabetes, 13% with gestational diabetes mellitus, and 12% with an undisclosed type of diabetes) completed the survey. Access to ICT increased from 89% in 2012 to 97% in 2017. The most commonly owned device was a mobile phone (87% ownership in 2017). Increase in mobile Internet usage in the <40 years of age subgroup was significant (P = 0.04). Significant increases in Internet access and smartphone feature use were observed in patients aged ≥40 years (P ≤0.001 for all). Overall use of short message service (SMS, or text messaging) was high (90 and 80% for ages <40 and ≥40 years, respectively). Use of digital applications was low, even among the young (45% in 2017). Comfort with online consultations (40%) and support groups (32%) was also low. CONCLUSION: Access to and acceptance and use of ICT is high, especially in those <40 years of age; however, the greatest increases were seen in those aged ≥40 years. High penetrance of mobile phones and text messaging in all age-groups would suggest that innovations involving an SMS platform have the greatest potential to enhance diabetes care.

Maternal vs paternal diabetes: The parental history is different in younger onset versus older onset type 2 diabetes.

BACKGROUND: A number of previous studies exploring family history of type 2 diabetes have reported a predominance of maternal diabetes. These studies have not explicitly compared parental history of diabetes across the spectrum of disease onset from youth to later adulthood. METHODS: Family history data from 11,467 patients with type 2 diabetes were extracted from the RPA Diabetes Centre database. Parental histories of diabetes were compared across a range of age of diagnosis strata (15-<30, 30-<40, 40-<50, 50-<60 and 60-<70 years). For the young-onset group (diagnosed between 15 and 30 years of age), associations between parental history of diabetes and the presence of cardio-metabolic risk factors and diabetic complications were also explored. RESULTS: For the total cohort and within each age of diagnosis strata, more individuals reported maternal history than paternal history of diabetes. The young-onset group demonstrated the highest prevalence of any parental history of diabetes (60.7%), the highest combined maternal and paternal history (15.8%) and the smallest differential between maternal (25.1%) and paternal (19.7%) history of diabetes. Within the young-onset group, no significant association between parental history and cardio-metabolic risk factors or diabetic complications were identified after a median of 15.0 years of diabetes exposure. CONCLUSION: Overall, our results demonstrate a consistent maternal excess of diabetes which could be consistent with an underlying epigenetic effect. However, the differential between maternal and paternal history is significantly lower in the young-onset group. Earlier emergence of type 2 diabetes may therefore reflect a different interaction and impact of genetic and environmental factors.

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.

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.

Monocyte CD163 is altered in association with diabetic complications: possible protective role.

The scavenger receptor CD163 is exclusively expressed by monocyte/macrophages and is shed by matrix metalloproteinases (MMPs) and neutrophil elastase (ELA2) as soluble CD163 (sCD163). Monocyte phenotype is altered in diabetes, but the relationship among monocyte CD163, sCD163, and diabetic complications is not known and was investigated in this study. Blood was obtained from patients with diabetes for >10 yr and mice with diabetes for ≤20 wk. Blood from people and mice without diabetes acted as controls. The percentage of CD163+ monocytes and monocyte CD163 mRNA was determined by flow cytometry and qRT-PCR, respectively. Plasma sCD163, MMPs, and ELA2 were measured by ELISA. The ability of glucocorticoids to stimulate isolated monocyte CD163 expression was also investigated. The percentage of CD163+ monocytes was significantly decreased and sCD163 significantly increased (both P < 0.05) in patients with diabetes with complications compared to those without complications. Plasma ELA2 and MMP-3 were also increased (P < 0.05), but CD163 mRNA was unaltered. sCD163 correlated with worsening renal function, as determined by eGFR (r = -0.48, P < 0.05). In diabetic mice, increased sCD163 at wk 5 and decreased percentage of CD163+ monocytes at wk 10 preceded alteration in kidney collagen IV mRNA at wk 20 (all P < 0.05). In vitro incubation of monocytes in anti-inflammatory glucocorticoid increased the percentage of CD163+ monocytes (P < 0.05). In people, higher sCD163 and decreased percentage of CD163+ monocytes were consistent with increased monocyte activation and shedding. The murine data indicated that these changes preceded the development of diabetic complications. Taken together, these results suggest that higher circulating percentage of CD163+ monocytes may have anti-inflammatory effects and may protect from development of diabetic complications.

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.

Hypoglycaemia and QT interval prolongation: Detection by simultaneous Holter and continuous glucose monitoring.

This study using simultaneous Holter and continuous glucose monitoring demonstrates that prolongation of QT interval can occur with hypoglycaemia in an ambulatory setting in people with type 1 and type 2 diabetes treated with insulin. This highlights the potential proarrhythmic harms associated with hypoglycaemia.

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.

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.

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.

Impact of sociodemographic and diabetes-related factors on the presence and severity of depression in immigrant chinese Australian people with diabetes.

The coexistence of depression with diabetes significantly increases the likelihood of developing complications. This study aimed to describe the presence and severity of depression in immigrant Chinese Australian people with diabetes and explore its relationship to sociodemographic and diabetes-related factors. This study found that approximately one-fifth of immigrant Chinese Australian people with diabetes had symptoms consistent with moderate to severe depression and that individuals who are socially isolated and have more complex treatment and complications of diabetes are particularly at risk.

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.

How best to use partial meal replacement in managing overweight or obese patients with poorly controlled type 2 diabetes.

OBJECTIVE: To compare patient compliance and benefits, over 12 months, of 1 versus 2 partial meal replacement (PMR) for the management of overweight/obese subjects with inadequately controlled type 2 diabetes. DESIGN AND METHODS: Thirty-six overweight patients with inadequately controlled type 2 diabetes (BMI > 27 kg/m(2) and HbA1c > 7.5% [58 mmol/mol]) were randomized to receive 1 or 2 PMR/day, while maintaining usual lifestyle. Subjects were seen monthly and adjustment of medications was made to prevent hypoglycemia. Compliance was assessed by counting unused sachets. RESULTS: Patients on 2 PMR/day lost almost 4 kg compared with only 0.5 kg in the 1 PMR/day group. This difference was statistically significant (P < 0.05). Overall PMR was about 30% as effective as in our previous study on total meal replacement. Reductions in weight, waist, and HbA1c were better in the 2 PMR/day group while patient dropout and compliance were not worse over a 12-month period. CONCLUSION: PMR provides a further management option for overweight/obese individuals with type 2 diabetes. The initial recommendation should be 2 PMR/day.

Antenatal diagnosis of fetal genotype determines if maternal hyperglycemia due to a glucokinase mutation requires treatment.

OBJECTIVE: In women with hyperglycemia due to heterozygous glucokinase (GCK) mutations, the fetal genotype determines its growth. If the fetus inherits the mutation, birth weight is normal when maternal hyperglycemia is not treated, whereas intensive treatment may adversely reduce fetal growth. However, fetal genotype is not usually known antenatally, making treatment decisions difficult. HISTORY AND EXAMINATION: We report two women with gestational diabetes mellitus resulting from GCK mutations with hyperglycemia sufficient to merit treatment. INVESTIGATION: In both women, DNA from chorionic villus sampling, performed after high-risk aneuploidy screening, showed the fetus had inherited the GCK mutation. Therefore, maternal hyperglycemia was not treated. Both offspring had a normal birth weight and no peripartum complications. CONCLUSIONS: In pregnancies where the mother has hyperglycemia due to a GCK mutation, knowing the fetal GCK genotype guides the management of maternal hyperglycemia. Fetal genotyping should be performed when fetal DNA is available from invasive prenatal diagnostic testing.

Steroid-induced diabetes: is it just unmasking of type 2 diabetes?

Aims. We compared the demographic profile and clinical characteristics of individuals with new onset steroid-induced diabetes (NOSID) to Type 2 diabetes (T2DM) patients with and without steroid treatment. Methods. The demographic profile and clinical characteristics of 60 individuals who developed NOSID were examined and matched to 60 type 2 diabetes patients receiving steroid therapy (T2DM+S) and 360 diabetic patients not on steroids (T2DM) for age, duration of diabetes, HbA1c, gender, and ethnicity. Results. Patients who developed NOSID had less family history of diabetes (P ≤ 0.05) and were less overweight (P ≤ 0.02). NOSID was more commonly treated with insulin. Despite a matching duration of diabetes and glycaemic control, significantly less retinopathy was found in the group of patients with NOSID (P < 0.03). Conclusions. It appears that steroid treatment primarily precipitated diabetes in a group of individuals otherwise less affected by risk factors of diabetes at that point in time, rather than just opportunistically unmasking preexisting diabetes. Furthermore, the absence of retinopathy suggests that patients with NOSID had not been exposed to long periods of hyperglycaemia. However, the impact of the underlying conditions necessitating steroid treatment and concomitant medications such as immunosuppressants on diabetes development remain to be defined.

Alterations in monocyte CD16 in association with diabetes complications.

Monocytes express many cell surface markers indicative of their inflammatory and activation status. Whether these markers are affected by diabetes and its complications is not known and was investigated in this study. Blood was obtained from 22 nondiabetic and 43 diabetic subjects with a duration of diabetes >10 years, including 25 without and 18 with clinically significant complications. The number of CD45(+)CD14(+) monocytes and the percentage expressing the proinflammatory marker CD16 were determined by flow cytometry. Other markers of monocyte activation and expression of chemokine receptors were also examined. The relationship between monocyte CD16 and clinical data, selected cytokines, and chemokines was also investigated. Diabetes had no effect on total white cell number but increased monocyte number. Diabetes also significantly decreased the number of CD16(+) monocytes but only in those with diabetic complications. Other markers of monocyte activation status and chemokine receptors were not affected by diabetes or complications status. Diabetes induced plasma proinflammatory cytokines and they were lower in diabetic subjects with complications compared to those without complications. These results suggest that the circulating monocyte phenotype is altered by diabetic complications status. These changes may be causally related to and could potentially be used to predict susceptibility to diabetic complications.

Can common clinical parameters be used to identify patients who will need insulin treatment in gestational diabetes mellitus?

OBJECTIVE: To identify patients with gestational diabetes mellitus (GDM) who will need antenatal insulin treatment (AIT) by using a risk-prediction tool based on maternal clinical and biochemical characteristics at diagnosis. RESEARCH DESIGN AND METHODS: Data from 3,009 women attending the Royal Prince Alfred Hospital GDM Clinic, Australia, between 1995 and 2010 were studied. A risk engine was developed from significant factors identified for AIT using a logistic regression model. RESULTS: A total of 51% of GDM patients required AIT. Ethnicity, gestation at diagnosis, HbA(1c), fasting and 60-min glucose at oral glucose tolerance test, BMI, and diabetes family history were significant independent determinants of AIT. Notably, only 9% of the attributable risk for AIT can be explained by the clinical factors studied. A modeled risk-scoring system was therefore a poor predictor of AIT. CONCLUSIONS: Baseline maternal characteristics including HbA(1c) alone cannot predict the need for AIT in GDM. Lifestyle, compliance, or as yet unmeasured influences play a greater role in determining AIT.