COVID-19 vaccine-associated subacute thyroiditis: an unusual suspect for de Quervain's thyroiditis.

Subacute thyroiditis following vaccination is an uncommon presentation of thyrotoxicosis. As the world undertakes its largest immunisation campaign to date in an attempt to protect the population from COVID-19 infections, an increasing number of rare post vaccine side effects are being observed. We report a case of a middle-aged woman who presented with painful thyroid swelling following the second dose of the COVID-19 mRNA vaccine BNT162b2 (Pfizer-BioNTech) with clinical, biochemical and imaging features consistent with destructive thyrotoxicosis. Symptomatic management only was required for the self-limiting episode. Thyroiditis typically has a mild and self-limiting course and thus this observation should not deter people from vaccination, as COVID-19 infection has a far greater morbidity and mortality risk than thyroiditis.

Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications.

OBJECTIVE: To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. RESULTS: In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 27% lower (P = 2 × 10-39); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10-13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10-8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). CONCLUSIONS: These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.

Quantitative levels of serum N-glycans in type 1 diabetes and their association with kidney disease.

We investigated associations of quantitative levels of N-glycans with hemoglobin A1c (HbA1c), renal function and renal function decline in type 1 diabetes. We measured 46 total N-glycan peaks (GPs) on 1565 serum samples from the Scottish Diabetes Research Network Type 1 Bioresource Study (SDRNT1BIO) and a pool of healthy donors. Quantitation of absolute abundance of each GP used 2AB-labeled mannose-3 as a standard. We studied cross-sectional associations of GPs and derived measures with HbA1c, albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR), and prospective associations with incident albuminuria and final eGFR. All GPs were 1.4 to 3.2 times more abundant in SDRTN1BIO than in the healthy samples. Absolute levels of all GPs were slightly higher with higher HbA1c, with strongest associations for triantennary trigalactosylated disialylated, triantennary trigalactosylated trisialylated structures with core or outer arm fucose, and tetraantennary tetragalactosylated trisialylated glycans. Most GPs showed increased abundance with worsening ACR. Lower eGFR was associated with higher absolute GP levels, most significantly with biantennary digalactosylated disialylated glycans with and without bisect, triantennary trigalactosylated trisialylated glycans with and without outer arm fucose, and core fucosylated biantennary monogalactosylated monosialylated glycans. Although several GPs were inversely associated prospectively with final eGFR, cross-validated multivariable models did not improve prediction beyond clinical covariates. Elevated HbA1c is associated with an altered N-glycan profile in type 1 diabetes. Although we could not establish GPs to be prognostic of future renal function decline independently of HbA1c, further studies to evaluate their impact in the pathogenesis of diabetic kidney disease are warranted.

Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes. METHODS: We used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records. RESULTS: Median age was 44.1 years and diabetes duration 20.9 years. The prevalence of CKD stages G1, G2, G3 and G4 and end-stage renal disease (ESRD) was 64.0%, 29.3%, 5.4%, 0.6%, 0.7%, respectively. Micro/macroalbuminuria prevalence was 8.6% and 3.0%, respectively. The incidence rate of ESRD was 2.5 (95% CI 1.9, 3.2) per 1000 person-years. The majority (59%) of those with chronic kidney disease stages G3-G5 did not have albuminuria on the day of recruitment or previously. Over 11.6 years of observation, the median annual decline in eGFR was modest at -1.3 ml min-1 [1.73 m]-2 year-1 (interquartile range [IQR]: -2.2, -0.4). However, 14% experienced a more significant loss of at least 3 ml min-1 [1.73 m]-2. These decliners had more cardiovascular disease (OR 1.9, p = 5 × 10-5) and retinopathy (OR 1.3 p = 0.02). Adding HbA1c, prior cardiovascular disease, recent mean eGFR and prior trajectory of eGFR to a model with age, sex, diabetes duration, current eGFR and ACR maximised the prediction of final eGFR (r2 increment from 0.698 to 0.745, p < 10-16). Attempting to model nonlinearity in eGFR decline or to detect latent classes of decliners did not improve prediction. CONCLUSIONS: These data show much lower levels of kidney disease than historical estimates. However, early identification of those destined to experience significant decline in eGFR remains challenging.

Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes.

BACKGROUND: The objective of this cross-sectional study was to explore the relationship of detectable C-peptide secretion in type 1 diabetes to clinical features and to the genetic architecture of diabetes. METHODS: C-peptide was measured in an untimed serum sample in the SDRNT1BIO cohort of 6076 Scottish people with clinically diagnosed type 1 diabetes or latent autoimmune diabetes of adulthood. Risk scores at loci previously associated with type 1 and type 2 diabetes were calculated from publicly available summary statistics. RESULTS: Prevalence of detectable C-peptide varied from 19% in those with onset before age 15 and duration greater than 15 years to 92% in those with onset after age 35 and duration less than 5 years. Twenty-nine percent of variance in C-peptide levels was accounted for by associations with male gender, late age at onset and short duration. The SNP heritability of residual C-peptide secretion adjusted for gender, age at onset and duration was estimated as 26%. Genotypic risk score for type 1 diabetes was inversely associated with detectable C-peptide secretion: the most strongly associated loci were the HLA and INS gene regions. A risk score for type 1 diabetes based on the HLA DR3 and DQ8-DR4 serotypes was strongly associated with early age at onset and inversely associated with C-peptide persistence. For C-peptide but not age at onset, there were strong associations with risk scores for type 1 and type 2 diabetes that were based on SNPs in the HLA region but not accounted for by HLA serotype. CONCLUSIONS: Persistence of C-peptide secretion varies widely in people clinically diagnosed as type 1 diabetes. C-peptide persistence is influenced by variants in the HLA region that are different from those determining risk of early-onset type 1 diabetes. Known risk loci for diabetes account for only a small proportion of the genetic effects on C-peptide persistence.

N-Glycan Profile and Kidney Disease in Type 1 Diabetes.

OBJECTIVE: Poorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes. RESEARCH DESIGN AND METHODS: Using serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG. RESULTS: Higher HbA1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 × 10-4). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 × 10-4). CONCLUSIONS: Higher HbA1c in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor-ß pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.

Severe hypercalcaemia secondary to isolated adrenocorticotrophic hormone deficiency and subacute thyroiditis.

Severe hypercalcaemia is usually due to either neoplastic disease or primary hyperparathyroidism. Rarer causes do exist, and exceptionally these may occur concomitantly. We describe the case of a 45-year-old man who presented in a debilitated state with severe hypercalcaemia (total serum calcium 3.56 mmol/L, albumin 35 g/L) and suppressed serum parathyroid hormone concentration. It was initially suspected that he had neoplastic disease, but routine thyroid function tests demonstrated evidence of thyrotoxicosis [thyroid-stimulating hormone <0.05 mU/L (0.15-3.5); free thyroxine 75 pmol/L (8-27); total tri-iodothyronine 7.0 nmol/L (1.0-2.6)], which was probably secondary to a silent or subacute thyroiditis. After extensive investigation, it was established that the patient also had isolated adrenocorticotrophic hormone deficiency, presumably secondary to lymphocytic hypophysitis. Glucocorticoid therapy resulted in a dramatic improvement in the patient's clinical state and 1 year later he remained euthyroid and normocalcaemic.