Durable change in glycaemic control following intensive management of type 2 diabetes in the ACCORD clinical trial

We aimed to determine the persistence of glycaemic control 1 year after a limited period of intensive glycaemic management of type 2 diabetes

Glucose testing and insufficient follow-up of abnormal results: a cohort study

BACKGROUND: More than 6 million Americans have undiagnosed diabetes. Several national organizations endorse screening for diabetes by physicians, but actual practice is poorly understood. Our objectives were to measure the rate, the predictors and the results of glucose testing in primary care, including rates of follow-up for abnormal values. METHODS: We conducted a retrospective cohort study of 301 randomly selected patients with no known diabetes who received care at a large academic general internal medicine practice in New York City. Using medical records, we collected patients' baseline characteristics in 1999 and followed patients through the end of 2002 for all glucose tests ordered. We used multivariate logistic regression to measure associations between diabetes risk factors and the odds of glucose testing. RESULTS: Three-fourths of patients (78%) had at least 1 glucose test ordered. Patient age (≥45 vs. <45 years), non-white ethnicity, family history of diabetes and having more primary care visits were each independently associated with having at least 1 glucose test ordered (p < 0.05), whereas hypertension and hyperlipidemia were not. Fewer than half of abnormal glucose values were followed up by the patients' physicians. CONCLUSION: Although screening for diabetes appears to be common and informed by diabetes risk factors, abnormal values are frequently not followed up. Interventions are needed to trigger identification and further evaluation of abnormal glucose tests

Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC

OBJECTIVE The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS The strongest associations in the MHC class II region (rs3957146, beta [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (beta [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, beta [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.Peer reviewe

First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes

OBJECTIVELatent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODSWe performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396).RESULTSThe leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.CONCLUSIONSOur results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.Peer reviewe

Durable change in glycaemic control following intensive management of type 2 diabetes in the ACCORD clinical trial

AIMS/HYPOTHESIS: We aimed to determine the persistence of glycaemic control 1 year after a limited period of intensive glycaemic management of type 2 diabetes. METHODS: 4119 ACCORD Trial participants randomized to target HbA(1c) <6.0% (42 mmol/mol) for 4.0±1.2 years were systematically transitioned to target HbA(1c) 7.0–7.9% (53–63 mmol/mol) and followed for an additional 1.1±0.2 years. Characteristics of participants with HbA(1c) <6.5% (48 mmol/mol) or ≥6.5% at transition were compared. Changes in BMI and glucose-lowering medications were compared between those ending with HbA(1c) <6.5% vs ≥6.5%. Poisson models were used to assess the independent effect of attaining HbA(1c) <6.5% before transition on ending with HbA(1c) <6.5%. RESULTS: Participants with pre-transition HbA(1c) <6.5% were older with shorter duration diabetes and took less insulin but more non-insulin glucose-lowering agents than those with higher HbA(1c). A total of 823 participants achieved a final HbA(1c) <6.5%, and had greater post-transition reductions in BMI, insulin dose and secretagogue and acarbose use than those with higher HbA(1c) (p<0.0001). HbA(1c) <6.5% at transition predicted final HbA(1c) <6.5% (crude RR 4.9 [95% CI 4.0, 5.9]; RR 3.9 [95% CI 3.2, 4.8] adjusted for demographics, co-interventions, pre-intervention HbA(1c), BMI and glucose-lowering medication, and post-transition change in both BMI and glucose-lowering medication). Progressively lower pre-transition HbA(1c) levels were associated with a greater likelihood of maintaining a final HbA(1c) of <6.5%. Follow-up duration was not associated with post-transition rise in HbA(1c). CONCLUSIONS/INTERPRETATION: Time-limited intensive glycaemic management using a combination of agents that achieves HbA(1c) levels below 6.5% in established diabetes is associated with glycaemic control more than 1 year after therapy is relaxed