Clinical characteristics and outcomes of COVID-19 patients with prediabetes.

BACKGROUND AND AIMS: We aimed to examine the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) patients with prediabetes. METHODS: This was a retrospective cohort study of 102 COVID-19 patients admitted to a tertiary care hospital in India between May and October 2020. RESULTS: Most patients had a poor clinical profile on admission. They had high rates of invasive mechanical ventilation (48%), intensive care unit admission (48%), complications (72.6%), and mortality (32.4%). CONCLUSION: People with prediabetes are at high risk for poor outcomes from COVID-19.

COVID-19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission.

AIM: To assess predictors of in-hospital mortality in people with prediabetes and diabetes hospitalized for COVID-19 infection and to develop a risk score for identifying those at the greatest risk of a fatal outcome. MATERIALS AND METHODS: A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID-19. The primary outcome was in-hospital mortality and the predictor variables upon admission included clinical data, co-morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in-hospital mortality. RESULTS: The mean age of people hospitalized (n = 238) for COVID-19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance (P = .128). A score including age, arterial occlusive disease, C-reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in-hospital mortality with a C-statistic of 0.889 (95% CI: 0.837-0.941) and calibration of 1.000 (P = .909). CONCLUSIONS: The in-hospital mortality for COVID-19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in-hospital mortality.

Clinical Characteristics and Outcomes of Patients With Diabetes Admitted for COVID-19 Treatment in Dubai: Single-Centre Cross-Sectional Study.

BACKGROUND: Recent studies have shown that diabetes is a major risk factor that contributes to the severity of COVID-19 and resulting mortality. Poor glycemic control is also associated with poor patient outcomes (eg, hospitalization and death). OBJECTIVE: This study aimed to describe the clinical characteristics and outcomes of patients with diabetes who were admitted to our hospital for COVID-19 treatment. METHODS: This cross-sectional, observational study comprised patients with diabetes admitted with COVID-19 to Mediclinic Parkview Hospital in Dubai, United Arab Emirates, from March 30 to June 7, 2020. We studied the differences among characteristics, length of hospital stay, diabetes status, comorbidities, treatments, and outcomes among these patients. RESULTS: Of the cohort patients, 25.1% (103/410) had coexistent diabetes or prediabetes. These patients represented 17 different ethnicities, with 59.2% (61/103) from Asian countries and 35% (36/103) from Arab countries. Mean patient age was 54 (SD 12.5) years, and 66.9% (69/103) of patients were male. Moreover, 85.4% (88/103) of patients were known to have diabetes prior to admission, and 14.6% (15/103) were newly diagnosed with either diabetes or prediabetes at admission. Most cohort patients had type 2 diabetes or prediabetes, and only 2.9% (3/103) of all patients had type 1 diabetes. Furthermore, 44.6% (46/103) of patients demonstrated evidence suggesting good glycemic control during the 4-12 weeks prior to admission, as defined arbitrarily by admission hemoglobin A1c level <7.5%, and 73.8% (76/103) of patients had other comorbidities, including hypertension, ischemic heart disease, and dyslipidemia. Laboratory data (mean and SD values) at admission for patients who needed ward-based care versus those who needed intensive care were as follows: fibrinogen, 462.8 (SD 125.1) mg/dL vs 660.0 (SD 187.6) mg/dL; D-dimer, 0.7 (SD 0.5) µg/mL vs 2.3 (SD 3.5) µg/mL; ferritin, 358.0 (SD 442.0) mg/dL vs 1762.4 (SD 2586.4) mg/dL; and C-reactive protein, 33.9 (SD 38.6) mg/L vs 137.0 (SD 111.7) mg/L. Laboratory data were all significantly higher for patients in the intensive care unit subcohort (P<.05). The average length of hospital stay was 14.55 days for all patients, with 28.2% (29/103) of patients requiring intensive care. In all, 4.9% (5/103) died during hospitalization-all of whom were in the intensive care unit. CONCLUSIONS: Majority of patients with diabetes or prediabetes and COVID-19 had other notable comorbidities. Only 4 patients tested negative for COVID-19 RT-PCR but showed pathognomonic changes of COVID-19 radiologically. Laboratory analyses revealed distinct abnormal patterns of biomarkers that were associated with a poor prognosis: fibrinogen, D-dimer, ferritin, and C-reactive protein levels were all significantly higher at admission in patients who subsequently needed intensive care than in those who needed ward-based care. More studies with larger sample sizes are needed to compare data of COVID-19 patients admitted with and without diabetes within the UAE region.

Implications of COVID-19 Pandemic on Evolution of Diabetes in Malaria-Endemic African Region.

The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.

High prevalence of insulin resistance and occurrence prior to hyperinsulinemia threshold among people living with HIV in Pune, India.

BACKGROUND: Diabetes prevalence in HIV is not well characterized for India, despite the high burden of both individual diseases. Epidemiology of insulin resistance (IR): a precursor to diabetes, and its associated risk factors are also poorly understood in Asian Indian people living with HIV (PLHIV). We assessed the prevalence of diabetes and IR in Pune, India and the associated risk factors for IR. METHODS: Cross-sectional analysis of adult (≥18 years) PLHIV receiving care at Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, India (BJGMC- SGH). Proportions and medians of PLHIV characteristics by diabetes status and IR were described. Homeostatic Model Assessment (HOMA) index value ≥2 was used to define IR. Line of least squares assessed the relationship between IR and hyperinsulinemia. Association between sociodemographic, clinical factors with IR was determined using logistic regression. RESULTS: Of 485 enrollees, 47% were men, median age was 40 years (IQR: 35-46), median CD4 counts were 389 cells/mm3 (246-609). Thirty-five percent were centrally obese, 75% were adherent to WHO recommended physical activity guidelines. Prevalence of diabetes, prediabetes, IR were 9%, 16% and 38%, respectively. Twenty-nine percent non-diabetics had IR and it occurred much prior to the threshold for hyperinsulinemia. IR was associated with the use of ART drugs (OR: 6.6, 95% CI: 2.9-15.2 and 5.4, 95% CI: 2.2-13.6 for first- and second line ART respectively) and central obesity (OR:1.9, 95% CI: 1.1-3.4). CONCLUSIONS: One fourth of the study population was diabetic or prediabetic and more than a third had IR. Better understanding of diabetes disease progression in relation to IR and the effect of physical activity on central obesity among Asian Indian PLHIV is mandated.

Diabetes mellitus in HIV-infected patients: fasting glucose, A1c, or oral glucose tolerance test - which method to choose for the diagnosis?

BACKGROUND: Antiretroviral therapy dramatically reduced HIV-related morbidity and mortality, prolonging the lifespan of HIV-infected patients. Greater duration of infection and exposure to antiretroviral therapy makes these patients susceptible to traditional cardio-metabolic risk factors and pathologies. The optimal diagnostic protocol for Diabetes Mellitus in these patients is still controversial. Haemoglobin A1c (HbA1c) has been shown to underestimate glycaemia levels and the oral glucose tolerance test (OGTT) has been shown to reveal cases of glucose metabolism disturbances in patients with normal fasting glucose. Thus, this study aimed to determine the prevalence of prediabetes and diabetes in a population of HIV-infected patients undergoing combined antiretroviral therapy, using three different diagnostic methods (fasting glucose, OGTT and HbA1c), to determine the agreement between the different methods and the characteristics associated with each one. METHODS: This study analyzed 220 HIV-infected patients on antiretroviral therapy. Patient characteristics were collected using a standardized protocol. Disturbances of glucose homeostasis were defined by the ADA 2017 criteria. Patients were characterized according to the presence or absence of clinical lipodystrophy, and distributed into four different categories, according to the presence, or absence of either clinical lipoatrophy, or abdominal prominence. Insulin resistance was assessed by HOMA-IR and QUICKI indexes. Agreement between the diagnostic methods was assessed by Cohen's kappa coefficient. RESULTS: There were no patients diagnosed with diabetes with HbA1c. 5.9% prevalence was obtained when OGTT was used, and 3.2% prevalence when fasting glucose was used. Prediabetes had a prevalence of 14.1% when using HbA1c, 24.1% when using OGTT, and 20% when using fasting glucose. In all three methods, glucose homeostasis disturbances were associated with older age and higher resistance to insulin. Regarding other characteristics, associations varied between the three methods. The agreement between them was fair, or slight. CONCLUSIONS: We observed that HbA1c was the method that diagnosed the least amount of cases and that OGTT was the one that diagnosed the most cases. Accordingly, our results indicate that HbA1c underestimated glycaemia levels in this population and that the use of OGTT might allow an earlier diagnosis of glucose homeostasis disturbances, potentially making it possible to avoid severe complications of DM.

Hepatitis C virus induces a prediabetic state by directly impairing hepatic glucose metabolism in mice.

Virus-related type 2 diabetes is commonly observed in individuals infected with the hepatitis C virus (HCV); however, the underlying molecular mechanisms remain unknown. Our aim was to unravel these mechanisms using FL-N/35 transgenic mice expressing the full HCV ORF. We observed that these mice displayed glucose intolerance and insulin resistance. We also found that Glut-2 membrane expression was reduced in FL-N/35 mice and that hepatocyte glucose uptake was perturbed, partly accounting for the HCV-induced glucose intolerance in these mice. Early steps of the hepatic insulin signaling pathway, from IRS2 to PDK1 phosphorylation, were constitutively impaired in FL-N/35 primary hepatocytes via deregulation of TNFα/SOCS3. Higher hepatic glucose production was observed in the HCV mice, despite higher fasting insulinemia, concomitant with decreased expression of hepatic gluconeogenic genes. Akt kinase activity was higher in HCV mice than in WT mice, but Akt-dependent phosphorylation of the forkhead transcription factor FoxO1 at serine 256, which triggers its nuclear exclusion, was lower in HCV mouse livers. These findings indicate an uncoupling of the canonical Akt/FoxO1 pathway in HCV protein-expressing hepatocytes. Thus, the expression of HCV proteins in the liver is sufficient to induce insulin resistance by impairing insulin signaling and glucose uptake. In conclusion, we observed a complete set of events leading to a prediabetic state in HCV-transgenic mice, providing a valuable mechanistic explanation for HCV-induced diabetes in humans.

No Ljungan virus RNA in stool samples from the Norwegian environmental triggers of type 1 diabetes (MIDIA) cohort study.

OBJECTIVE: Ljungan virus (LjV) has been proposed as a potential environmental factor for type 1 diabetes. The objective was to test for any association of LjV with type 1 diabetes. RESEARCH DESIGN AND METHODS: A nested case-control design was used to test for any association between the development of pre-diabetic autoimmunity and presence of LjV in stool samples (n = 3,803) in the Norwegian Environmental Triggers of Type 1 Diabetes (MIDIA) study. The children followed were 27 infants who developed pre-diabetic autoimmunity during or shortly after the sampling period, 54 matched control subjects, and 94 other children. RESULTS: No LjV RNA was detected. CONCLUSIONS: The results indicate that LjV is rare in young children. LjV does not seem to be involved in the development of human type 1 diabetes.

Cure of prediabetic mice by viral infections involves lymphocyte recruitment along an IP-10 gradient.

Viruses can cause but can also prevent autoimmune disease. This dualism has certainly hampered attempts to establish a causal relationship between viral infections and type 1 diabetes (T1D). To develop a better mechanistic understanding of how viruses can influence the development of autoimmune disease, we exposed prediabetic mice to various viral infections. We used the well-established NOD and transgenic RIP-LCMV models of autoimmune diabetes. In both cases, infection with the lymphocytic choriomeningitis virus (LCMV) completely abrogated the diabetic process. Interestingly, such therapeutic viral infections resulted in a rapid recruitment of T lymphocytes from the islet infiltrate to the pancreatic draining lymph node, where increased apoptosis was occurring. In both models this was associated with a selective and extensive expression of the chemokine IP-10 (CXCL10), which predominantly attracts activated T lymphocytes, in the pancreatic draining lymph node, and in RIP-LCMV mice it depended on the viral antigenic load. In RIP-LCMV mice, blockade of TNF-alpha or IFN-gamma in vivo abolished the prevention of T1D. Thus, virally induced proinflammatory cytokines and chemokines can influence the ongoing autoaggressive process beneficially at the preclinical stage, if produced at the correct location, time, and levels.

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children.

Enterovirus infections are a potential environmental trigger of the autoimmune process leading to clinical type 1 diabetes. It has been suggested that the risk of virus-induced beta-cell damage might be connected with a defect in humoral immune responsiveness to enteroviruses. In the present study we assessed whether such a defect in IgG responsiveness to coxsackievirus B4 antigen existed in young children who developed diabetes-associated autoantibodies during prospective observation from birth until the age of 18 months. IgG levels and maturation of antibody avidity were analysed in 21 children with autoantibodies and 41 control children who had experienced an equal number of enterovirus infections and were additionally matched for age, sex and HLA-DQB1 risk alleles for type 1 diabetes but had not produced diabetes-associated autoantibodies. IgG levels to coxsackievirus B4 were high in cord serum reflecting the presence of maternal antibodies. Mean IgG levels gradually decreased but began to increase after the age of 6 months, showing no significant difference between autoantibody positive and control children. The avidity of antibodies was strong in cord serum and decreased gradually during the first year of life when maternal antibodies disappeared. The avidity indices, which varied considerably from child to child, did not differ between the autoantibody-positive and -negative subjects. In conclusion, our data suggest that children affected by a beta-cell damaging autoimmune process show normal responses to coxsackievirus B4 antigens.

Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group.

In a prospective multicentre study described previously on prediabetic events in siblings of index cases with insulin-dependent diabetes mellitus, 31 children developed clinical diabetes during the observation period and 51 children seroconverted for islet cell antibodies or insulin autoantibodies. By using nonserotype specific EIA and RIA, it has shown recently that enterovirus infections in both groups were frequently associated with increases of islet cell antibody and/or insulin autoantibody titres. Serum specimens sequentially collected from 12 children during the prediabetic period were still available and were then tested for serotype-specific neutralizing antibodies. Plaque-neutralization assays were carried out for coxsackievirus A9, coxsackievirus B types 1 to 6, and echovirus types 1 and 11. An unequivocal monotypic increase in neutralizing antibodies was observed on seven occasions in six children, on one occasion with coxsackievirus A9, one with coxsackievirus B1, two with coxsackievirus B2, two with coxsackievirus B3, and one with coxsackievirus B5. In four patients, the infection was associated temporally with increases in the levels of islet cell antibodies, insulin autoantibodies and/or antibodies to glutamic acid decarboxylase, and in three other patients, it coincided with the clinical onset of insulin-dependent diabetes mellitus. These results suggest that the association of enterovirus infections with insulin-dependent diabetes mellitus is not restricted to serotype 4 of coxsackie B viruses suspected previously, but that several different serotypes might play a role in the pathogenesis of the disease.