Effects of long-term HbA1c variability on serious infection risks in patients with type 2 diabetes and the influence of age, sex and ethnicity: A cohort study of primary care data.

AIMS: Long-term HbA1c (glycated haemoglobin) variability is associated with micro- and macrovascular complications in Type 2 diabetes (T2D). We explored prospective associations between HbA1c variability and serious infections, and how these vary by HbA1c level, age, sex and ethnicity. METHODS: 411,963 T2D patients in England, aged 18-90, alive on 01/01/2015 in the Clinical Practice Research Datalink with ≥ 4 HbA1c measurements during 2011-14. Poisson regression estimated incidence rate ratios (IRRs) for infections requiring hospitalisation during 2015-19 by HbA1c variability score (HVS) and average level, adjusting for confounders, and stratified by age, sex, ethnicity and average level. Attributable risk fractions (AF) were calculated using reference categories for variability (HVS < 20) and average level (42-48 mmol/mol). RESULTS: An increased infection risk (IRR > 1.2) was seen with even modest variability (HVS ≥ 20, 73 % of T2D patients), but only at higher average levels (≥64 mmol/mol, 27 % patients). Estimated AFs were markedly greater for variability than average level (17.1 % vs. 4.1 %). Associations with variability were greater among older patients, and those with lower HbA1c levels, but not observed among Black ethnicities. CONCLUSIONS: HbA1c variability between T2D patients' primary care visits appears to be associated with more serious infections than average level overall. Well-designed trials could test whether these associations are causal.

A matched cohort study evaluating the risks of infections in people with type 1 diabetes and their associations with glycated haemoglobin.

AIMS: People with type 1 diabetes (T1D) have raised infection rates compared to those without, but how these risks vary by age, sex and ethnicity, or by glycated haemoglobin (HbA1c), remain uncertain. METHODS: 33,829 patients with T1D in Clinical Practice Research Datalink on 01/01/2015 were age-sex-ethnicity matched to two non-diabetes patients. Infections were collated from primary care and linked hospitalisation records during 2015-2019, and incidence rate ratios (IRRs) were estimated versus non-diabetes. For 26,096 people with T1D, with ≥3 HbA1c measurements in 2012-2014, mean and coefficient of variation were estimated, and compared across percentiles. RESULTS: People with T1D had increased risk for infections presenting in primary care (IRR = 1.81, 95%CI 1.77-1.85) and hospitalisations (IRR = 3.37, 3.21-3.53) compared to non-diabetes, slightly attenuated after further adjustment. Younger ages and non-White ethnicities had greater relative risks, potentially explained by higher HbA1c mean and variability amongst people with T1D within these sub-groups. Both mean HbA1c and greater variability were strongly associated with infection risks, but the greatest associations were at the highest mean levels (hospitalisations IRR = 4.09, 3.64-4.59) for >97 versus ≤53 mmol/mol. CONCLUSIONS: Infections are a significant health burden in T1D. Improved glycaemic control may reduce infection risks, while prompter infection treatments may reduce hospital admissions.

IVF/ICSI in a woman with active acromegaly: successful outcome following treatment with pegvisomant.

A 29 year old woman with difficult to control acromegaly and a pituitary macroadenoma responded to pegvisomant therapy and subsequently conceived with her first cycle of in-vitro fertilization and intra-cytoplasmic sperm injection. Pregnancy was complicated by gestational diabetes, pituitary gland enlargement and deteriorating visual fields. Conservative management with elective cesarean section was performed at 32 weeks gestation. A healthy boy was delivered who remains developmentally normal at 1 year. This complex case required intricate care by a multi-disciplinary team and is likely to represent the first in many cases of assisted conception on pegvisomant therapy for active acromegaly.

Plasminogen activator inhibitor-1 (PAI-1) activity post myocardial infarction: the role of acute phase reactants, insulin-like molecules and promoter (4G/5G) polymorphism in the PAI-1 gene.

High PAI-1 levels post acute myocardial infarction (AMI) are associated with a poor outcome. Concentrations of insulin-like molecules, proinflammatory cytokines and an insertion (5G)/deletion (4G) polymorphism in the promoter of the PAI-1 gene, all influence circulating PAI-1 levels. We studied the determinants of PAI-1 in 123 patients immediately following and at 6 months after AMI. Within 24 h of AMI, PAI-1 levels were related to those of proinsulin-like molecules but not to levels of cytokines (interleukin-1beta, interleukin-6 or tumour necrosis factor-alpha), to genotype, or to interactions between genotype and cytokine concentration. PAI-1 levels 6 months after AMI were related to concentrations of interleukin-1beta but not to genotype. We have found no evidence that subjects with the 4G/4G polymorphism have higher PAI-1 levels on admission or 6 months after AMI. In these patients, levels of PAI-1 are related to concentrations of proinsulin-like molecules and of proinflammatory cytokines.