Heterogeneity in presentation of hyperglycaemia during COVID-19 pandemic: A proposed classification.

Diabetes and hyperglycemia occurring during COVID-19 era have implications for COVID-19 related morbidity/mortality. In this brief review, we have attempted to categorise and classify such heterogenous hyperglycemic states. During COVID-19 pandemic broadly two types of hyperglycemia were seen: one in patients without COVID-19 infection and second in patients with COVID-19 infection. Patients not inflicted with COVID-19 infection and diagnosed with either type 2 diabetes mellitus (T2DM) or type 1 diabetes mellitus (T1DM) show more severe hyperglycemia and more ketoacidosis, respectively. In former, it could be attributed to weight gain, decreased exercise, stress and in both type of diabetes, due to delayed diagnosis during lockdown and pandemic. In patients with COVID-19 and associated pneumonia, altered glucose metabolism leading to hyperglycemia could be due to corticosteroids, cytokine storm, damage to pancreatic beta cells, or combination of these factors. Some of these patients present with diabetic ketoacidosis, hyperglycemic hyperosmolar state or both. We have provided a framework for categorisation of hyperglycemic states, which could be consolidated/revised in future based on new research data.

Clinical profiles of hyperglycemic crises: A single-center retrospective study from Japan.

AIMS/INTRODUCTION: The aim of the present study was to clarify the pathophysiologies of hyperglycemic crises in Japanese patients. MATERIALS AND METHODS: This was a retrospective study of patients with hyperglycemic crises admitted to Kumamoto Medical Center, Kumamoto, Japan, between 2012 and 2019. Patients were classified as having diabetic ketoacidosis (DKA), hyperglycemic hyperosmotic syndrome (HHS) or a mixed state of the two conditions (MIX), and laboratory data and levels of consciousness at hospital admission, as well as the rates of mortality and coagulation disorders, were compared. RESULTS: The diagnostic criteria for hyperglycemic crisis were met in 144 cases, comprising 87 (60.4%), 38 (26.4%) and 19 (13.2%) cases of DKA, HHS and MIX, respectively. Type 1 diabetes was noted in 46.0 and 26.3% of patients in the DKA and MIX groups, respectively. Fibrin degradation product and D-dimer levels were significantly higher in the HHS group than in the DKA group (DKA and HHS groups: fibrin degradation product 7.94 ± 8.43 and 35.54 ± 51.80 µg/mL, respectively, P < 0.01; D-dimer 2.830 ± 2.745 and 14.846 ± 21.430 µg/mL, respectively, P < 0.01). Mortality rates were 5.7, 13.2 and 5.3% in the DKA, HHS and MIX groups, respectively. Seven patients (4.9%), four of whom were in the MIX group, had acute arterial occlusive diseases. CONCLUSIONS: The low frequency of type 1 diabetes in DKA and MIX might be responsible for reduced insulin secretion in Japanese populations. Patients with hyperglycemic crises have increased coagulability, and acute arterial occlusion needs to be considered, particularly in MIX.

Evidence to support the classification of hyperglycemia first detected in pregnancy to predict diabetes 6-12 weeks postpartum: A single center cohort study.

AIMS: Diagnostic criteria for type 2 diabetes mellitus (T2DM) applied to women with gestational diabetes mellitus (GDM) may predict postpartum T2DM but requires validation. METHODS: Women with GDM aged ≥ 18-years were prospectively evaluated 6-12 weeks after delivery at Tygerberg Hospital, Cape Town, South-Africa (November 2015- December 2018). Glucose status at GDM diagnosis was categorized into i) International Association for Diabetes in Pregnancy Study Group (IADPSG) T2DM (fasting glucose ≥ 7 mmol/L and/or 2hr-glucose ≥ 11.1 mmol/L) or ii) modified National Institute for Care Excellence (NICE) GDM (fasting glucose ≥ 5.6 mmol/L-6.9 mmol/L and/or 2hr-glucose ≥ 7.8 mmol/L-11 mmol/L) and compared with postpartum OGTT. RESULTS: IADPSG T2DM and NICE GDM was present in 35% (n = 64) and 65% (n = 117) of the 181 women who completed the 8 ± 2 weeks postpartum evaluation respectively. Postpartum, the prevalence of T2DM and prediabetes was 26% (n = 47/181) and 15% (n = 28). Antenatal IADPSG T2DM categorization identified 31/47 women with postpartum T2DM (sensitivity 75%; specificity 48%). All of the modified NICE GDM category women who developed T2DM (n = 16/117) had elevations of both fasting and 2hr-glucose values antenatally. CONCLUSION: The utility of the IADPSG T2DM criteria to predict T2DM postpartum is confirmed. Women with both fasting and 2hr-glucose values above GDM cut-offs emerged as another high-risk category.

Hyperglycemia, Classified with Multiple Biomarkers Simultaneously in Men without Diabetes, and Risk of Fatal Prostate Cancer.

The association between hyperglycemia and prostate cancer risk is inconsistent, and its association with prostate cancer mortality is understudied. Thus, we investigated the association between hyperglycemia and prostate cancer risk and mortality using multiple biomarkers simultaneously to classify hyper- and normoglycemia. We conducted a prospective analysis of 5,162 cancer-free men attending visit 2 (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study followed for total (N = 671) and lethal (N = 69) prostate cancer incidence and prostate cancer mortality (N = 64) through 2012. Men without diagnosed diabetes were classified as normo- or hyperglycemic using joint categories of fasting glucose, glycated hemoglobin, and glycated albumin (or fructosamine) defined by clinical or research cutpoints. We evaluated the multivariable-adjusted association of hyperglycemia with prostate cancer incidence and mortality using Cox proportional hazards regression; men with diagnosed diabetes were included as a separate exposure category. Among 4,753 men without diagnosed diabetes, 61.5% were classified as having hyperglycemia (high on ≥1 biomarker). HbA1c and glycated albumin together classified 61.9% of 1,736 men with normal fasting glucose as normoglycemic. Compared with men who were normal on all three biomarkers, men who were high on ≥1 biomarker had an increased risk of lethal [HR, 2.50; 95% confidence interval (CI), 1.12-5.58] and fatal (HR, 3.20; 95% CI, 1.26-8.48) disease, but not total prostate cancer incidence (HR, 0.98; 95% CI, 0.81-1.20); associations were similar including fructosamine instead of glycated albumin. Our findings indicate hyperglycemia is associated with an increased risk of lethal and fatal prostate cancer, but not total prostate cancer incidence.

Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia.

There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (ß = 0.151, P = 0.035) and HOMA-IR (ß = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes.

HYPERGLYCEMIA MANAGEMENT IN PATIENTS WITH POSTTRANSPLANTATION DIABETES.

OBJECTIVE: Posttransplantation diabetes (PTDM) is a common occurrence after solid-organ transplantation and is associated with increased morbidity, mortality, and health care costs. There is a limited number of studies addressing strategies for hyperglycemia management in this population, with a few articles emerging recently. METHODS: We performed a PubMed search of studies published in English addressing hyperglycemia management of PTDM/new-onset diabetes after transplant (NODAT). Relevant cited articles were also retrieved. RESULTS: Most of the 25 publications eligible for review were retrospective studies. Insulin therapy during the early posttransplantation period showed promise in preventing PTDM development. Thiazolidinediones have been mostly shown to exert glycemic control in retrospective studies, at the expense of weight gain and fluid retention. Evidence with metformin, sulfonylureas, and meglitinides is very limited. Incretins have shown promising results in small prospective studies using sitagliptin, linaglitpin, and vildagliptin and a case series using liraglutide. CONCLUSION: Prospective randomized studies assessing the management of hyperglycemia in PTDM are urgently needed. In the meantime, clinicians need to be aware of the high risk of PTDM and associated complications and current concepts in management.

The classification of hospitalized patients with hyperglycemia and its implication on outcome: results from a prospective observational study in Internal Medicine.

The relevance of classifying hyperglycemic hospitalized subjects (HS) as known diabetes (D), newly discovered diabetes (ND), and stress hyperglycemia (SH) is unclear. The aim of this study was to determine the prevalence, in-hospital mortality, and length of stay (LOS) of three different phenotypes of HS. Fasting glucose ≥126 mg/dL (7 mmol/L) or random blood glucose ≥200 mg/dL (11.1 mmol/L) defined HS who were categorized into three groups: D; ND (no history of diabetes and HbA1c ≥48 mmol/mol); SH (no history of diabetes and HbA1c <48 mmol/mol). The end points of the study were in-hospital mortality and LOS. Of 1447 consecutive enrolled subjects, the prevalence of HS was 28.6 % (415/1447), of these 71.6 % had D, 21.2 % SH, and 7.2 % ND, respectively. In-hospital death was 3.9 % in normoglycemic and 6.0 % in hyperglycemic subjects. Individuals with SH had an increased risk of in-hospital death (7.9 %) (HR 2.17, 95 % CI 1.18-4.9; p = 0.039), while this was not observed for D and ND patients. The mean LOS was greater in ND and SH subjects. Hyperglycemia is common, and is associated with an increased risk of in-hospital mortality and extension of hospital stay. HbA1c along with clinical history is a useful tool to identify subgroups of hyperglycemic hospitalized subjects. Individuals with SH have a longer LOS, and a double risk of in-hospital mortality. Additionally, identifying previously unknown diabetes represents a remarkable opportunity for prevention of diabetes-related acute and chronic complications.

Strategies for implementing the WHO diagnostic criteria and classification of hyperglycaemia first detected in pregnancy.

The World Health Organization (WHO) has recently released updated recommendations on Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy which are likely to increase the prevalence of gestational diabetes mellitus (GDM). Any increase in the number of women with GDM has implications for health services since these women will require treatment and regular surveillance during the pregnancy. Some health services throughout the world may have difficulty meeting these demands since country resources for addressing the diabetes burden are finite and resource allocation must be prioritised by balancing the need to improve care of people with diabetes and finding those with undiagnosed diabetes, including GDM. Consequently each health service will need to assess their burden of hyperglycaemia in pregnancy and decide if and how it will implement programmes to test for and treat such women. This paper discusses some considerations and options to assist countries, health services and health professionals in these deliberations.

Systematic review of descriptive cohort studies on the dynamics of glycaemia among adults admitted to hospital with acute stroke.

AIM: This article presents the results of a systematic review of descriptive cohort studies on the dynamics of glycaemia among adults admitted to hospital with acute stroke. BACKGROUND: Hyperglycaemia is common among adults admitted to hospital with stroke. DESIGN: Systematic review. DATA SOURCES: A search for descriptive cohort studies published between January 1996-June 2011, was conducted in MEDLINE, PubMed and Embase electronic databases. The search was performed using the terms 'stroke', 'hyperglycaemia' and/or 'glucose' combined and limited to adults and English language publications. Searching of citations from identified studies supplemented the electronic searches. REVIEW METHODS: A systematic review was conducted of eight studies, meeting the criteria of: (1) descriptive cohort studies; (2) adults admitted to hospital with acute stroke; and (3) glycaemic status monitored over at least two consecutive days from admission to hospital. The review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis standards. RESULTS: The dynamics of glycaemia after stroke has been investigated in seven prospective cohort studies and one retrospective study. The patterns that emerged were persisting normoglycaemia, transient hyperglycaemia, persisting hyperglycaemia and delayed hyperglycaemia. Surges in glycaemia are likely on days 2 and 3 and some adults will not exhibit hyperglycaemia till day 7. CONCLUSION: Further large cohort studies are required to explore the dynamic of glycaemia after stroke for at least 1 week duration. The timing of formal screening for diabetes mellitus is important, as early screening may overestimate detection rates.

What level of hyperglycaemia on admission indicates a poor prognosis in patients with myocardial infarction treated invasively?

BACKGROUND: Stress hyperglycaemia on admission is a predictor of mortality in patients with acute myocardial infarction (MI). AIM: To establish what level of hyperglycaemia on admission indicates a significantly poorer long-term prognosis in patients with MI treated invasively. METHODS: Glycaemia on admission was measured in patients with both ST-segment elevation MI (STEMI) and non-ST- -segment elevation MI (NSTEMI) treated with percutaneous coronary intervention (PCI). In-hospital and late mortality were evaluated during a 679.3 ± 202 day follow-up. RESULTS: We enrolled 794 patients (564 men; 71%), mean age 63.8 ± 11.3 years. One per cent of the patients died during initial hospitalisation, and 10% during the two-year follow-up. The mean value of glycaemia in the whole population was 115 ± 36 mg/dL (6.32 ± 1.98 mmol/L). Admission glycaemia in patients who died in hospital was 194 ± 71 mg/dL (10.67 ± 3.91 mmol/L), while in the patients discharged home it was 114 ± 35 mg/dL (6.27 ± 1.93 mmol/L) (p 〈 0.0001). In terms of two-year mortality, the patients who died had also significantly higher glycaemia on admission (145 ± 48 mg/dL; 7.98 ± 2.64 mmol/L) vs 112 ± 31 mg/dL (6.16 ± 1.71 mmol/L, p 〈 0.0001). Apart from admission hyperglycaemia, we found the following risk factors of late mortality in univariate analysis: age, heart rate (HR), left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), creatinine level, number of significantly narrowed coronary vessels other than the infarct related artery (IRA), and unsuccessful PCI. In multivariate analysis, the following parameters correlated with death in the two-year follow-up: glycaemia on admission, age, HR, LVEF, GFR, creatinine level, total cholesterol, number of significantly narrowed coronary vessels other than the IRA, and unsuccessful PCI. Hyperglycaemia on admission was an independent risk factor of death even after adjustment for confounding variables such as age, sex and LVEF. We compared the areas under ROC curve for in-hospital mortality and the areas under ROC curve for late mortality according to glycaemia on admission. Both were significantly different from those of a random model (p 〈 0.001 and p 〈 0.001, respectively). A glycaemia value of 205 mg/dL (11.28 mmol/L) calculated from ROC curve had the highest sensitivity and specificity for late mortality. Apart from these findings, we observed a linear correlation between glycaemia and mortality. CONCLUSIONS: The best cut-off value for stress hyperglycaemia determined by ROC curve in patients with acute MI treated invasively is 205 mg/dL (11.28 mmol/L). Patients with glucose levels 〉 205 mg/dL (11.28 mmol/L) on admission have significantly higher late mortality compared to those with glucose levels 〈 205 mg/dL (11.28 mmol/L). Our results suggest that hyperglycaemia is a reliable marker of poor outcome in acute MI patients with and without previously diagnosed diabetes mellitus. This level of glucose may be used in risk stratification in patients with acute MI.

Call for consistent coding in diabetes mellitus using the Royal College of General Practitioners and NHS pragmatic classification of diabetes.

BACKGROUND: The prevalence of diabetes is increasing with growing levels of obesity and an aging population. New practical guidelines for diabetes provide an applicable classification. Inconsistent coding of diabetes hampers the use of computerised disease registers for quality improvement, and limits the monitoring of disease trends. OBJECTIVE: To develop a consensus set of codes that should be used when recording diabetes diagnostic data. METHODS: The consensus approach was hierarchical, with a preference for diagnostic/disorder codes, to define each type of diabetes and non-diabetic hyperglycaemia, which were listed as being completely, partially or not readily mapped to available codes. The practical classification divides diabetes into type 1 (T1DM), type 2 (T2DM), genetic, other, unclassified and non-diabetic fasting hyperglycaemia. We mapped the classification to Read version 2, Clinical Terms version 3 and SNOMED CT. RESULTS: T1DM and T2DM were completely mapped to appropriate codes. However, in other areas only partial mapping is possible. Genetics is a fastmoving field and there were considerable gaps in the available labels for genetic conditions; what the classification calls 'other' the coding system labels 'secondary' diabetes. The biggest gap was the lack of a code for diabetes where the type of diabetes was uncertain. Notwithstanding these limitations we were able to develop a consensus list. CONCLUSIONS: It is a challenge to develop codes that readily map to contemporary clinical concepts. However, clinicians should adopt the standard recommended codes; and audit the quality of their existing records.

Global adaptation of IADPSG recommendations: a national approach.

The current practice for diagnosing gestational diabetes mellitus (GDM) in Israel employs a two-step screening approach using a 50 g glucose challenge test (GCT) followed by a 3-hour 100 g oral glucose tolerance test (OGTT). The overall adherence to this process is more than 90%. Recently, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommended changing this practice to a single-step GDM screening, employing a 75 g OGTT. New plasma glucose cutoffs were recommended. To make recommendations for a new screening and diagnosis policy for GDM in Israel, a committee was assembled, including representatives of professional medical organizations, health maintenance organizations (HMOs), health policy makers, epidemiologists and biostatisticians. There was agreement that a consensus can be achieved only by clinical evidence and that consensus is a key factor for changing health policy. It was also realized that the availability of local data on the annual rates of GDM, its complications, and cost-effectiveness of screening and treatment are suboptimal. This generated two studies: the first provided additional analyses of data concerning Israeli women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, and the second was a cost-effectiveness analysis based on Clalit Health Service's (the largest HMO in the country) database. We found that the prevalence of GDM in Israel is approximately 6% and is expected to increase to 9% by adopting the new IADPSG recommendations. The conclusion was that a one-step approach is presumed to be not only cost-effective but cost-saving, even under conservative estimates. We recommend such a process for other countries debating whether to change their GDM screening and diagnostic approach.

Matching diagnosis and management of diabetes in pregnancy to local priorities and resources: an international approach.

The International Association of the Diabetes and Pregnancy Study Groups' (IADPSG) criteria for the diagnosis and classification of hyperglycemia in pregnancy are described and application of these in differing healthcare contexts on a worldwide basis is reported. Existing local protocols and known epidemiologic and clinical data regarding the detection and management of overt diabetes and gestational diabetes in the context of human pregnancy are considered. Although the IADPSG criteria are uniform, their introduction poses a variety of practical and technical challenges in differing healthcare contexts, both between and within countries. Knowledge of local factors will be vital in the implementation of the new guidelines and will require extensive liaison with local clinical and health policy groups. Resource availability will be critical in determining the type of treatment available in this context. The IADPSG criteria offer an important opportunity for a uniform approach to diabetes in pregnancy. Scaled implementation of these criteria adapted to a variety of local healthcare contexts should improve both research endeavors and patient care.

Identification of persons with dysglycemia: terminology and practical significance.

Allocating scarce resources for dysglycemia intervention requires identification of persons who will benefit. Identification has two steps: screening followed by diagnosis. Lowering a screening test's cut-off score identifies more persons with dysglycemia, but causes more normoglycemic persons to receive diagnostic testing. Raising a test's cut-off score reduces needless diagnostic testing, but increases the number falsely identified as not having dysglycemia. With limited budgets for intervention, raising a screening test's cut-off score may be appropriate. With ample budgets, lowering the test's cut-off score may be appropriate. Screening tests are most efficient in populations with high prevalence of dysglycemia.