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Aims/hypothesis: The aim of this work was to describe the clinical characteristics of adults with type 1 diabetes admitted to hospital and the risk factors associated with severe coronavirus disease-2019 (COVID-19) in the UK., Methods: A retrospective cohort study was performed using data collected through a nationwide audit of people admitted to hospital with diabetes and COVID-19, conducted by the Association of British Clinical Diabetologists from March to October 2020. Prespecified demographic, clinical, medication and laboratory data were collected from the electronic and paper medical record systems of the participating hospitals by local clinicians. The primary outcome of the study, severe COVID-19, was defined as death in hospital and/or admission to the adult intensive care unit (AICU). Logistic regression models were used to generate age-adjusted ORs., Results: Forty UK centres submitted data. The final dataset included 196 adults who were admitted to hospital and had both type 1 diabetes and COVID-19 on admission (male sex 55%, white 70%, with mean [SD] age 62 [19] years, BMI 28.3 [7.3] kg/m 2 and last recorded HbA 1c 76 [31] mmol/mol [9.1 (5.0)%]). The prevalence of pre-existing microvascular disease and macrovascular disease was 56% and 39%, respectively. The prevalence of diabetic ketoacidosis on admission was 29%. A total of 68 patients (35%) died or were admitted to AICU. The proportions of people that died were 7%, 38% and 38% of those aged <55, 55-74 and ≥75 years, respectively. BMI, serum creatinine levels and having one or more microvascular complications were positively associated with the primary outcome after adjusting for age., Conclusions/interpretation: In people with type 1 diabetes and COVID-19 who were admitted to hospital in the UK, higher BMI, poorer renal function and presence of microvascular complications were associated with greater risk of death and/or admission to AICU. Risk of severe COVID-19 is reassuringly very low in people with type 1 diabetes who are under 55 years of age without microvascular or macrovascular disease. IN PEOPLE WITH TYPE 1 DIABETES AND COVID-19 ADMITTED TO HOSPITAL IN THE UK, BMI AND ONE OR MORE MICROVASCULAR COMPLICATIONS HAD A POSITIVE ASSOCIATION AND LOW SERUM CREATINE LEVELS HAD A NEGATIVE ASSOCIATION WITH DEATH/ADMISSION TO INTENSIVE CARE UNIT AFTER ADJUSTING FOR AGE.

Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements. In 265 Pima Indians (133 diabetic, 132 non-diabetic, 129 male, 136 female, male, mean age 46.6, range 34-68 years) the promoter genotype frequencies were 23.0% for 4G/4G, 49.8% for 4G/5G and 27.2% for 5G/5G compared to 35.4%, 50.8% and 13.8% respectively, (chi 2 = 15.3, 2 df, p < 0.0005) previously reported in Caucasians with NIDDM. The mean plasma activity levels in the three genotypes in the Pima Indians were 18.2, 19.1 and 18.1 U/ml, respectively. Plasminogen activator inhibitor-1 activities correlated with plasma insulin (r = 0.38, p < 0.0001), body mass index (r = 0.24, p < 0.0001), and with triglyceride level (r = 0.12, p = 0.054) but there was no relationship between promotor genotype and activity. A steeper regression slope between plasminogen activator inhibitor-1 activity and triglycerides has been observed in Caucasians with the 4G/4G genotype as compared to Caucasians with the other genotypes. This was not found in the Pima population which may indicate a functional difference in this gene associated with reduced cardiovascular risk and may be involved in the lack of association of plasminogen activator inhibitor-1 levels with NIDDM in Pima Indians.

Risk factors predicting deterioration to diabetes mellitus were examined in 181 subjects with impaired glucose tolerance. Fifty-seven subjects had impaired glucose tolerance on one occasion followed by normal glucose tolerance at a repeat oral glucose tolerance test, and 124 subjects had impaired glucose tolerance on two successive oral glucose tolerance tests. Subjects were followed for a median period of 5.0 years (range 1.0-17.2). The age- and sex-adjusted cumulative incidence of diabetes at 10 years of follow-up was higher in subjects who had impaired glucose tolerance on both tests (70%) than in those whose glucose tolerance was normal at the repeat test (53%), [rate ratio (RR) = 1.6, 95% confidence intervals (CI) = 1.0-2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat oral glucose tolerance test) for subsequent diabetes, and incidence rate ratios were calculated for the 90th percentile compared with the 10th percentile of each continuous variable for the whole group. In all subjects, in separate models, higher body mass index [RR = 2.0, 95% CI = 2.2-9.9], high fasting serum insulin concentrations [RR = 2.4, 95% CI = 1.4-4.2], and low early insulin response [RR = 0.5, 95% CI = 0.3-0.8] 30 min after a glucose load were significant predictors for deterioration to diabetes. In a multivariate analysis which controlled for age and sex, 120-min post-load glucose, fasting insulin and late insulin response predicted diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32-33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay ("immunoreactive insulin") in 51 Type 2 (non-insulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of "immunoreactive insulin" as measured by standard radioimmunoassay and triglyceride (rs = 0.42, p less than 0.001), total cholesterol (rs = 0.25, p = 0.038), high density lipoprotein cholesterol (rs = -0.30, p = 0.018) and body mass index (rs = 0.30, p = 0.017), but only the relationships with triglyceride (rs = 0.36, p = 0.006) and body mass index (rs = 0.26, p = 0.34) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32-33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (rs = 0.33, p = 0.009), total cholesterol (rs = 0.23, p = 0.050), and plasminogen activator inhibitor (rs = 0.26, p = 0.049), and negatively with high density lipoprotein cholesterol (rs = -0.29, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)