Metformin mitigates insulin signaling variations induced by COVID-19 vaccine boosters in type 2 diabetes (preprint)

Diabetes is associated with an increased risk of Coronavirus disease 2019 (COVID-19) vulnerability and mortality. COVID-19 vaccines significantly reduce the risks of serious COVID-19 outcomes, but the impact of COVID-19 vaccines including their effectiveness and adverse effects in patients with diabetes are not well known yet. Here, we showed that 61.1% patients with type 2 diabetes, but not healthy controls, exhibited aggravated insulin resistance towards the booster shots of the COVID-19 vaccine. Furthermore, we showed that COVID-19 vaccination once a week also impaired insulin sensitivity in healthy mice after four weeks. We further showed that metformin, a common anti-diabetic medication, improved the impaired insulin signaling induced by COVID-19 vaccination in mice. This study suggests clinical implications for the close monitoring of glycemic control in diabetic patients after receiving COVID-19 vaccines and indicates the beneficial action of metformin in counteracting insulin signaling variations induced by COVID-19 vaccination in diabetic patients.

Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients.

Traditionally a disease of adults, type 2 diabetes (T2D) has been increasingly diagnosed in youth, particularly among adolescents and young adults of minority ethnic groups. Especially, during the recent COVID-19 pandemic, obesity and prediabetes have surged not only in minority ethnic groups but also in the general population, further raising T2D risk. Regarding its pathogenesis, a gradually increasing insulin resistance due to central adiposity combined with a progressively defective ß-cell function are the main culprits. Especially in youth-onset T2D, a rapid ß-cell activity decline has been observed, leading to higher treatment failure rates, and early complications. In addition, it is well established that both the quantity and quality of food ingested by individuals play a key role in T2D pathogenesis. A chronic imbalance between caloric intake and expenditure together with impaired micronutrient intake can lead to obesity and insulin resistance on one hand, and ß-cell failure and defective insulin production on the other. This review summarizes our evolving understanding of the pathophysiological mechanisms involved in defective insulin secretion by the pancreatic islets in youth- and adult-onset T2D and, further, of the role various micronutrients play in these pathomechanisms. This knowledge is essential if we are to curtail the serious long-term complications of T2D both in pediatric and adult populations.

Effect of circulating ceramides on adiposity and insulin resistance in patients with type 2 diabetes: An observational cross-sectional study.

INTRODUCTION: Insulin resistance (IR) is one of the common chronic metabolic disorders in Africa and elsewhere. Accumulation of lipids in the body may be due to an imbalance in the metabolism of lipids, glucose and proteins. Ceramides are a sphingolipid class of lipids that are biologically active and vital in the production of more complex lipids. Circulating ceramides are thought to have a role in the development of obesity-related IR, although the precise involvement remains unclear. AIM: To investigate the impact of circulating ceramide on IR and body adiposity in people with and without type 2 diabetes mellitus (T2DM). METHODOLOGY: The study was observational and cross-sectional. There were a total of 84 volunteers with T2DM and 75 nondiabetics (control). The participants' ages, body mass indexes (BMI), waist circumferences, and blood pressure (BP) were among the clinical parameters assessed. Ceramide levels, fasting plasma glucose (FPG), lipids, basal insulin levels and glycated haemoglobin (HbA1c) were also measured. Additionally, the homeostatic model assessment for IR (HOMA-IR) and beta cell function (HOMA-ß) were computed. RESULTS: T2DM and control participants had different mean values for anthropometric parameters, BP, FPG, HbA1c, lipids, insulin, HOMA-IR, HOMA-ß and ceramide levels (p < .05 for all). HOMA-IR, HOMA-ß and cardiovascular risk were significant correlates with ceramide levels in the T2DM group (r = 0.24; -0.34; 0.24, p < .05, respectively). Further, FPG (OR = 1.83, p = .01) and ceramide (OR = 1.05, p = .01) levels were significant predictors of IR in the case group. CONCLUSION: Patients with T2DM exhibited high ceramide concentrations, which, when combined with high FPG, were associated with IR. The consequences of circulating ceramides in health and disease; however, merit further research.

Ethnic differences in complement system biomarkers and their association with metabolic health in men of Black African and White European ethnicity.

Inflammation plays a fundamental role in the development of several metabolic diseases, including obesity and type 2 diabetes (T2D); the complement system has been implicated in their development. People of Black African (BA) ethnicity are disproportionately affected by T2D and other metabolic diseases but the impact of ethnicity on the complement system has not been explored. We investigated ethnic differences in complement biomarkers and activation status between men of BA and White European (WE) ethnicity and explored their association with parameters of metabolic health. We measured a panel of 15 complement components, regulators, and activation products in fasting plasma from 89 BA and 96 WE men. Ethnic differences were statistically validated. Association of complement biomarkers with metabolic health indices (BMI, waist circumference, insulin resistance, and HbA1c) were assessed in the groups. Plasma levels of the key complement components C3 and C4, the regulators clusterin and properdin and the activation marker iC3b were significantly higher in BA compared to WE men after age adjustment, while FD levels were significantly lower. C3 and C4 levels positively correlated with some or all markers of metabolic dysfunction in both ethnic groups while FD was inversely associated with HbA1c in both groups, and clusterin and properdin were inversely associated with some markers of metabolic dysfunction only in the WE group. Our findings of increased levels of complement components and activation products in BA compared to WE men suggest differences in complement regulation that may impact susceptibility to poor metabolic health.

Primary hyperparathyroidism in young patients is associated with metabolic disorders: a prospective comparative study.

BACKGROUND: Components of metabolic syndrome can be observed in patients with primary hyperparathyroidism (PHPT). The link between these disorders remains unclear due to the lack of relevant experimental models and the heterogeneity of examined groups. The effect of surgery on metabolic abnormalities is also controversial. We conducted a comprehensive assessment of metabolic parameters in young patients with PHPT. METHODS: One-center prospective comparative study was carried out. The participants underwent a complex biochemical and hormonal examination, a hyperinsulinemic euglycemic and hyperglycemic clamps, a bioelectrical impedance analysis of the body composition before and 13 months after parathyroidectomy compared to sex-, age- and body mass index matched healthy volunteers. RESULTS: 45.8% of patients (n = 24) had excessive visceral fat. Insulin resistance was detected in 54.2% of cases. PHPT patients had higher serum triglycerides, lower M-value and higher C-peptide and insulin levels in both phases of insulin secretion compared to the control group (p < 0.05 for all parameters). There were tendencies to decreased fasting glucose (p = 0.031), uric acid (p = 0.044) and insulin levels of the second secretion phase (p = 0.039) after surgery, but no statistically significant changes of lipid profile and M-value as well as body composition were revealed. We obtained negative correlations between percent body fat and osteocalcin and magnesium levels in patients before surgery. CONCLUSION: PHPT is associated with insulin resistance that is the main risk factor of serious metabolic disorders. Surgery may potentially improve carbohydrate and purine metabolism.

A clinical trial on anti-diabetic efficacy of submerged culture medium of Ceriporia lacerata mycelium.

BACKGROUND: Increased glucose level and insulin resistance are major factors in Type 2 diabetes mellitus (T2M), which is chronic and debilitating disease worldwide. Submerged culture medium of Ceriporia lacerata mycelium (CLM) is known to have glucose lowering effects and improving insulin resistance in a mouse model in our previous studies. The main purpose of this clinical trial was to evaluate the functional efficacy and safety of CLM in enrolled participants with impaired fasting blood sugar or mild T2D for 12 weeks. METHODS: A total of 72 participants with impaired fasting blood sugar or mild T2D were participated in a randomized, double-blind, placebo-controlled clinical trial. All participants were randomly assigned into the CLM group or placebo group. Fasting blood glucose (FBG), HbA1c, insulin, C-peptide, HOMA-IR, and HOMA-IR by C-peptide were used to assess the anti-diabetic efficacy of CLM for 12 weeks. RESULTS: In this study, the effectiveness of CLM on lowering the anti-diabetic indicators (C-peptide levels, insulin, and FBG) was confirmed. CLM significantly elicited anti-diabetic effects after 12 weeks of ingestion without showing any side effects in both groups of participants. After the CLM treatment, FBG levels were effectively dropped by 63.9% (ITT), while HOMA-IR level in the CLM group with FBG > 110 mg/dL showed a marked decrease by 34% up to 12 weeks. Remarkably, the effect of improving insulin resistance was significantly increased in the subgroup of participants with insulin resistance, exhibiting effective reduction at 6 weeks (42.5%) and 12 weeks (61%), without observing a recurrence or hypoglycemia. HbA1c levels were also decreased by 50% in the participants with reduced indicators (FBG, insulin, C-peptide, HOMA-IR, and HOMA-IR). Additionally, it is noteworthy that the levels of insulin and C-peptide were significantly reduced despite the CLM group with FBG > 110 mg/dL. No significant differences were detected in the other parameters (lipids, blood tests, and blood pressure) after 12 weeks. CONCLUSION: The submerged culture medium of CLM showed clinical efficacy in the improvement of FBG, insulin, C-peptide, HbAc1, and HOMA-index. The microbiome-based medium could benefit patients with T2D, FBG disorders, or pre-diabetes, which could guide a new therapeutic pathway in surging the global diabetes epidemic.

COVID-19 induced Diabetes: A novel presentation.

INTRODUCTION: The COVID-19 pandemic disproportionately affected patients who had comorbid diabetes mellitus. COVID-19 patients with diabetes experience significantly higher rates of complications and mortality. COVID-induced diabetes is a novel phenomenon observed in critically ill patients. The aims of this review were to explore the literature about COVID-induced diabetes and the pathophysiological mechanisms that could lead to this novel presentation. METHODS: A literature search was performed using PUBMED, Google Scholar, MEDLINE and Embase for original studies (meta-analyses, cross-sectional studies, case series, case reports) about new-onset diabetes following COVID infection, and the proposed biochemical pathways behind this presentation. It was assumed that the authors of the studies used the current diagnostic criteria for diagnosis of type 1 and type 2 diabetes. RESULTS: COVID-19 causes dysregulation of glucose homeostasis leading to new-onset diabetes and hyperglycaemia. This is also seen in patients with no previous risk factors for diabetes mellitus. The atypical glycaemic parameters and increased rates of DKA suggest that COVID-induced diabetes is a novel form of diabetes. A spectrum of COVID-induced diabetes has also been noted. COVID-induced diabetes is associated with remarkably higher mortality rates and worse outcomes compared to COVID-19 patients with pre-existing diabetes. The novel presentation of COVID-induced diabetes could be due to beta cell damage and insulin resistance caused by SARS-CoV-2. CONCLUSION: COVID-induced diabetes is essential to detect early, owing to its implications on prognosis. Further studies must include follow-up of these patients to better understand the trajectory of COVID-induced diabetes and the best management plan. It is also important to assess the beta cell function and insulin resistance of COVID-induced diabetes patients over time to better understand the underlying biochemical mechanisms.

Post-COVID-19 syndrome and insulin resistance 20 months after a mild COVID-19 (preprint)

Objective SARS-CoV-2 infection is associated with impaired glucose metabolism. Although the mechanisms are not fully understood, insulin resistance (IR) appears to be a central factor. Patients who had a severe acute phase, but even asymptomatic or with mild COVID-19, have an increased risk of T2DM. After the acute phase, post-COVID-19 syndrome (PCS) also seems to be related to this metabolic disturbance, but there is a paucity of studies. This study aims to evaluate a possible relationship between PCS and IR after mild COVID-19 and, if confirmed, whether there are differences by sex. Subjects and methods Retrospective observational cohort study including subjects who had mild COVID-19 between April and September 2020 in a community setting. None had been vaccinated against SARS-CoV-2 at inclusion, and previous T2DM and liver disease were exclusion criteria. Patients who met NICE criteria were classified as PCS+. Epidemiological and laboratory data were analysed. Three assessments were performed: 1E (pre-COVID-19, considered baseline and reference for comparisons), 2E (approximately 3 months after the acute phase), and 3E (approximately 20 months after the acute phase). A triglyceride-to-glucose (TyG) index [≥]8.74 was considered IR. Albumin-to-globulin ratio (AGR) and lactate dehydrogenase (LDH) were assessed as inflammatory markers. Bivariate analyses were performed, using nonparametric and repeated measures tests. A subsample without metabolic disorder or CVD (age< median, BMI<25 kg/m^2, elevated AGR, TyG index=7.80 [0.5]) was generated to reasonably rule out prior baseline IR that could bias the results. The relationships between PCS and TyG in 3E (TyG3) were modeled in 8 multiple regressions, stratifying by sex and BMI combinations. Results A total of 112 subjects (median [IQR] of age= 44 [20] years; 65 women) were analysed. Up to 14.3% was obese and 17% was hypertensive. Significant increases between 1E and 3E were registered regarding (i) basal glycemia (BG), 87 [14] mg/dL vs. 89 [14]; p=0.014, (ii) TyG index (8.25 [0.8] vs. 8.32 [0.7]; p=0.002), and (iii) LDH in 3rd tertile (16.1% vs 32.1%; p=0.007). A total of 8 previously normoglycemic subjects, showed BG2 or BG3 >126 mg/dL. The subgroups with IR highest prevalence at 3E were those of BMI [≥]25 kg/m^2 and PCS+. The subgroup without CVD presented a significant increase in the TyG index (TyG1=7.80 [0.1] vs. TyG3= 8.28 [0.1]; p=0.017). LDH1 was significantly correlated with TyG3 in both sexes (rho=0.214 in women, rho=0.298 in men); in contrast, LDH2 and LDH3 did not present such an association. In multivariable analysis, PCS has shown to be an independent and predictive variable of TyG index in women with BMI<25 kg/m^2, after adjustment for age, hypertension, BMI, Charlson comorbidity index, AGR1, AGR2, LDH1, number of symptoms of acute COVID-19, and number of days of the acute episode (beta coefficient=0.350; p=0.039). Conclusions PCS has played a secondary role in predicting IR, showing a modest effect compared to BMI or prior hypertension. A significant increase in IR has been noted 20 months after mild COVID-19, both in cases of previous baseline IR and in those without previous IR. Basal serum LDH has shown to be predictive of current TyG, regardless of elevated LDH after SARS-CoV-2 infection. There were profound differences between women and men, confirming the need for a sex-stratified analysis when addressing the relation between PCS and glycemic alterations.

Dietary Intervention on Overweight and Obesity after Confinement by COVID-19.

BACKGROUND: Obesity has become a public health problem in our society and is associated with many diseases, including type 2 diabetes mellitus, cardiovascular diseases, dyslipidemia, respiratory diseases, and cancer. Several studies relate weight loss in obese patients to improved anthropometric measurements and cardiometabolic risk. The objective of our study was to evaluate anthropometric changes, analytical parameters, insulin resistance, fatty liver, and metabolic scales, after a personalized weight loss program, through dietary advice to increase adherence to the Mediterranean diet and a motivational booster via mobile SMS messaging. METHODS: Intervention study on a sample of 1964 workers, in which different anthropometric parameters were evaluated before and after dietary intervention: the metabolic score of insulin resistance; non-alcoholic fatty liver disease using different scales; metabolic syndrome; atherogenic dyslipidemia; and the cardiometabolic index. A descriptive analysis of the categorical variables was performed, by calculating the frequency and distribution of the responses for each one. For quantitative variables, the mean and standard deviation were calculated, since they followed a normal distribution. Bivariate association analysis was performed by applying the chi-squared test (corrected by Fisher's exact statistic when conditions required it) and Student's t-test for independent samples (for comparison of means). RESULTS: The population subjected to the Mediterranean diet improved in all the variables evaluated at 12 months of follow-up and compliance with the diet. CONCLUSIONS: Dietary advice on a Mediterranean diet and its reinforcement with reminder messages through the use of mobile phones may be useful to improve the parameters evaluated in this study and reduce the cardiometabolic risk of patients.

The Effects of Viruses on Insulin Sensitivity and Blood-Brain Barrier Function.

In this review manuscript, we discuss the effects of select common viruses on insulin sensitivity and blood-brain barrier (BBB) function and the potential overlapping and distinct mechanisms involved in these effects. More specifically, we discuss the effects of human immunodeficiency virus (HIV), herpes, hepatitis, influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 viruses on insulin sensitivity and BBB function and the proposed underlying mechanisms. These viruses differ in their ability to be transported across the BBB, disrupt the BBB, and/or alter the function of the BBB. For RSV and SARS-CoV-2, diabetes increases the risk of infection with the virus, in addition to viral infection increasing the risk for development of diabetes. For HIV and hepatitis C and E, enhanced TNF-a levels play a role in the detrimental effects. The winter of 2022-2023 has been labeled as a tridemic as influenza, RSV, and COVID-19 are all of concern during this flu season. There is an ongoing discussion about whether combined viral exposures of influenza, RSV, and COVID-19 have additive, synergistic, or interference effects. Therefore, increased efforts are warranted to determine how combined viral exposures affect insulin sensitivity and BBB function.

Exercise modulation in inflammation and metabolic hormonal disorders of COVID-19 to decrease risk factors in coronary heart disease.

OBJECTIVES: Sedentary life style separated during COVID-19 pandemic. Patients with cardiovascular diseases (CVD) are vulnerable with sedentary life style. Therefore, the aim of this study was to investigate the effect of 8 weeks of combined and high intensity interval training (HIIT) on C Reactive protein, galectin-3, leptin, fibrinogen and insulin resistance index in coronary heart disease after COVID-19. METHODS: Thirty-six cardiovascular patients (55.14 ± 1.4 years, 78.6 ± 5.1 kg) were divided into three groups of combined exercise (n=13), HIIT (n=12) and control group (n=11). Combined exercise consisted of aerobic (4 weeks) and aerobic + HIIT exercise (4 weeks), three sessions per weeks. The protocol of the HIIT group included performing high intensity interval training, three sessions per weeks for 8 weeks. Blood samples were taken 24 h before the first training session and 48 h after the last training. C Reactive protein (CRP), galectin-3, leptin, fibrinogen measured with ELISA kit. RESULTS: CRP, galectin-3 and fibrinogen decreased significantly after 8 weeks of combined training and HIIT (compare to pre-test). Also, insulin resistance index after 8 weeks of combined exercise showed a significant decrease compare to pre-test (p<0.05). After 8 weeks, CRP, galectin-3 and insulin resistance significantly decreased compare to control group (p<0.05). CONCLUSIONS: In the patient with CVD, combined exercise training may be more effective than HIIT in reducing metabolic and heart risk factors after an epidemic such as COVID-19. However, change of leptin need to more studies.

The Validation Of Covid-19 information In The Pharmacoepidemiological Research Database for Public Health System by vaccination status (preprint)

Purpose: To validate Covid-19 information records in The Pharmacoepidemiological Research Database for Public Health System (BIFAP), commonly used for pharmacoepidemiological research in Spain. Methods: The recorded Covid-19 cases in primary care (PC) or positive test registries (gold-standard) were identified among vaccinated patients against SARS-CoV-2 infection of any age. They were matched with unvaccinated controls by birth year, vaccination date, region, and sex, between December 2020-October 2021. The sensitivity (SE), specificity (SP), positive (PPV), negative (NPV) predictive values, and date accurateness were estimated for PC by vaccination status and age brands. Results: Among 21,702 patients with positive tests and 20,866 with recorded Covid-19 diagnoses, the SE, SP, PPV, and NPV were, respectively, 79.98%, 99.95%, 80.24% and 99.94% among vaccinated, and 78.67%, 99.96%, 84.51% and 99.94% among controls. For those aged ≥70 years old, SE (71.15-72.85%) was lower while PPV (84.68-88.04%) was higher compared to <70 years old participants. 94.12% of the total true positive cases (N=17,191) were recorded within ±5 days from the date of the test result. Conclusions: PC Covid-19 diagnosis recorded in BIFAP showed high validation parameters. SE was similar and PPV was slightly lower among vaccinated than unvaccinated controls. Correction of vaccines effectiveness estimates by such misclassification is recommended. Data shows the influence of age. Among the elderly, Covid-19 diagnosis was less recorded but when recorded is more accurate than among younger patients. These findings permit the design of informed algorithms for performing Covid-19-related research.

Parinaud’s syndrome caused by a cerebral infarction in a Covid positive child secondary to diabetic ketoacidosis (preprint)

Cerebral infarction is a very rare complication of diabetic ketoacidosis (DKA) which is a metabolic disorder caused by insulin deficiency. A previously healthy 6-year-old boy with a newly diagnosed Type 1 diabetes mellitus presented with a severe DKA. The patient, who tested positive for SARS-CoC-2 nasopharyngeal PCR, developed about 72 hours after admission a Parinaud’s syndrome (PS), also known as dorsal midbrain syndrome, which is described as an up-gaze saccadic paresis, a convergence-retraction nystagmus, a light-near dissociation of the pupils and occasionally a lid retraction. The brain magnetic resonance imaging revealed an ischemic infarction in the left thalamus and the thalamo-mesencephalic junction with a slight extension in the midbrain tegmentum. His symptoms improved gradually and at 3-weeks follow-up he had a full neuro-ophthalmological recovery. By describing a Parinaud syndrome as a neuro-ophthalmologic complication in diabetic ketoacidosis (DKA) crisis, which, to our best knowledge, has not been described yet, our case expands the knowledge of the neurological manifestations occurring in children during diabetic ketoacidosis and reiterates the importance to keep those patients under strict neurological monitoring for at least 72 hours, especially in severe DKA and to request early brain imaging for any child with neurological deterioration.

Pyroptosis and Insulin Resistance in Metabolic Organs.

Skeletal muscle serves as the optimal effective organ to balance glucose homeostasis, but insulin resistance (IR) in skeletal muscle breaks this balance by impeding glucose uptake and causes metabolic disorders. IR in skeletal muscle is caused by multiple factors, and it has been reported that systemic low-grade inflammation is related to skeletal muscle IR, though its molecular mechanisms need to be ulteriorly studied. Pyroptosis is a novel inflammatory-mediated type of cell death. It has recently been reported that pyroptosis is associated with a decline in insulin sensitivity in skeletal muscle. The appropriate occurrence of pyroptosis positively eliminates pathogenic factors, whereas its excessive activation may aggravate inflammatory responses and expedite disease progression. The relationship between pyroptosis and IR in skeletal muscle and its underlined mechanism need to be further illustrated. The role of pyroptosis during the process of IR alleviation induced by non-drug interventions, such as exercise, also needs to be clarified. In this paper, we review and describe the molecular mechanisms of pyroptosis and further comb the roles of its relevant key factors in skeletal muscle IR, aiming to propose a novel theoretical basis for the relationship between pyroptosis and muscle IR and provide new research targets for the improvement of IR-related diseases.

Severe COVID-19 associated hyperglycaemia is caused by beta cell dysfunction: a prospective cohort study (preprint)

Background Hyperglycaemia was shown to be among the features of severe acute COVID-19 infection both in the acute and convalescence period. Mechanisms contributing to its development and/or maintenance in a post-COVID phase are still unclear.  Materials and Methods Survivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: indirect calorimetry and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI), respectively. Resting energy expenditure (REE) was calculated using the Weir and Harris-Benedict equation and substrate preference using the respiratory quotient (RQ) and nitrogen losses.  Results Thirty-two patients (12 women) were available for the analyses at T0 and 26 at T6. Baseline examination was within 21±6.5 days after COVID-19 diagnosis. Patients were hypermetabolic at baseline (30.7 ± 4.3 kcal/kg lean mass/day, ~120% predicted values) but REE declined over the 6 months (ΔT6-T0 mean difference (95% CI): -5.4 (-6.8, -4.1) kcal/kg lean mass/day, p<0.0001). 20 patients at T0 and 13 patients at T6 had hyperglycemia. None of the patients had positive islet autoantibodies. Insulin sensitivity at T0 was comparable between hyperglycaemic (H) vs. normoglycaemic (N) patients (T0 ISIH=3.07 ± 1.18, ISIN=3.23 ± 1.72, p=0.66), whereas insulin response was lower in the H group only (DIH=3.19 ± 2.16 vs DIN=8.78 ± 6.37, p=0.005). Over the 6 months, IS improved in the H group (ΔT6-T0 mean difference for ISI (95% CI): 1.84 (0.45, 3.24), p=0.01)), whereas IGI and DI did not improve in either group.  Conclusions Severe COVID-19 infection was associated with hypermetabolism that did not persist over the follow-up. Patients were insulin resistant in the acute phase, but only those with insufficient insulin response developed hyperglycaemia. Insufficient beta cell response was a possible mechanism leading to hyperglycaemia.

Single-centre case-control study investigating the association between acanthosis nigricans, insulin resistance and type 2 diabetes in a young, overweight, UK population.

OBJECTIVE: To determine the extent to which the presence of acanthosis nigricans confers additional risk for insulin resistance, in addition to obesity alone (body mass index, BMI) within a young, overweight, UK population. RESEARCH DESIGN AND METHODS: Retrospective data were collected to compare the degree of insulin resistance within a sample of 94 young people with acanthosis nigricans, and a matched cohort of 94 participants with obesity alone. Insulin resistance was assessed by fasting glucose, fasting insulin and Homeostatic Model Assessment of insulin resistance (HOMA-IR) score (a mathematical model derived to measure insulin resistance). RESULTS: The acanthotic and control group were well matched for age, BMI, BMI SDS and sex, although the groups were not matched for ethnicity. The acanthotic group showed a significantly greater median fasting insulin (215 pmol/L), mean fasting glucose (4.7 mmol/L) and median HOMA-IR score (6.4), compared with the control group (126 pmol/L, 4.5 mmol/L and 3.7, respectively). The presence of acanthosis nigricans as an indicator of insulin resistance was found to have a positive predictive value of 81% (within this study population). CONCLUSION: Individuals with both acanthosis nigricans and obesity had significantly greater degrees of insulin resistance than individuals with obesity alone. The findings support the potential for acanthosis nigricans as a visible marker of type 2 diabetes in young people.

Associations of resting and peak fat oxidation with sex hormone profile and blood glucose control in middle-aged women.

BACKGROUND AND AIMS: Menopause may reduce fat oxidation. We investigated whether sex hormone profile explains resting fat oxidation (RFO) or peak fat oxidation (PFO) during incremental cycling in middle-aged women. Secondarily, we studied associations of RFO and PFO with glucose regulation. METHOD AND RESULTS: We measured RFO and PFO of 42 women (age 52-58 years) with indirect calorimetry. Seven participants were pre- or perimenopausal, 26 were postmenopausal, and nine were postmenopausal hormone therapy users. Serum estradiol (E2), follicle-stimulating hormone, progesterone, and testosterone levels were quantified with immunoassays. Insulin sensitivity (Matsuda index) and glucose tolerance (area under the curve) were determined by glucose tolerance testing. Body composition was assessed with dual-energy X-ray absorptiometry; physical activity with self-report and accelerometry; and diet, with food diaries. Menopausal status or sex hormone levels were not associated with the fat oxidation outcomes. RFO determinants were fat mass (ß = 0.44, P = 0.006) and preceding energy intake (ß = -0.40, P = 0.019). Cardiorespiratory fitness (ß = 0.59, P = 0.002), lean mass (ß = 0.49, P = 0.002) and physical activity (self-reported ß = 0.37, P = 0.020; accelerometer-measured ß = 0.35, P = 0.024) explained PFO. RFO and PFO were not related to insulin sensitivity. Higher RFO was associated with poorer glucose tolerance (ß = 0.52, P = 0.002). CONCLUSION: Among studied middle-aged women, sex hormone profile did not explain RFO or PFO, and higher fat oxidation capacity did not indicate better glucose control.

COVID-19 Exacerbates Insulin Resistance During Diabetic Ketoacidosis in Pediatric Patients With Type 1 Diabetes.

OBJECTIVE: Although mortality from coronavirus disease 2019 (COVID-19) among youth with type 1 diabetes is rare, severe acute respiratory syndrome coronavirus 2 is associated with increased pediatric hospitalizations for diabetic ketoacidosis (DKA). To clarify whether the relationship between COVID-19 and DKA is coincidental or causal, we compared tissue glucose disposal (TGD) during standardized treatment for DKA between pediatric patients with COVID-19 and those without COVID-19. RESEARCH DESIGN AND METHODS: We retrospectively compared TGD during standardized therapy for DKA in all children with preexisting type 1 diabetes with or without COVID-19. Cases were assessed beginning with the first case of COVID-19-positive DKA on 19 June 2020 through 2 February 2022. RESULTS: We identified 93 COVID-19-negative patients and 15 COVID-19-positive patients who were treated for DKA, with similar baseline characteristics between groups. Median TGD was 46% lower among patients who had COVID-19 compared with those who did not (P = 0.013). CONCLUSIONS: These results suggest that COVID-19 provokes a metabolic derangement over and above factors that typically contribute to pediatric DKA. These findings underscore the significant and direct threat posed by COVID-19 in pediatric type 1 diabetes and emphasize the importance of mitigation and monitoring including through vaccination as a primary prevention.

Are lipid ratios and triglyceride-glucose index associated with critical care outcomes in COVID-19 patients?

Lipid ratios and the triglyceride and glucose index (TyG) could be a simple biochemical marker of insulin resistance (IR). The current study was carried out to examine the correlation between triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C), total cholesterol to HDL-C (TC/HDL-C), low-density lipoprotein-cholesterol to HDL-C ratio (LDL-C/HDL-C), as well as TyG index with the severity and mortality of severe coronavirus disease 2019 (COVID-19). A total of 1228 confirmed COVID-19 patients were included in the current research. Regression models were performed to evaluate the correlation between the lipid index and severity and mortality of COVID-19. The TyG index and TG/HDL-C levels were significantly higher in the severe patients (P<0.05). TG/HDL-C, LDL-C/HDL-C, TC/HDL-C ratios, and TyG index were significantly lower in survivor cases (P<0.05). Multivariate logistic regression analysis demonstrated that predictors of the severity adjusted for age, sex and BMI were TyG index, TG/HDL-C ratio (OR = 1.42 CI:1.10-1.82, OR = 1.06 CI: 1.02-1.11, respectively). This analysis showed that TG/HDL-C, TC/HDL-C, LDL-C/HDL-C ratios, and TyG index statistically are correlated with COVID-19 mortality (OR = 1.12 CI:1.06-1.18, OR = 1.24 CI:1.05-1.48, OR = 1.47 CI:1.19-1.80, OR = 1.52 CI:1.01-2.31, respectively). In summary, the TyG index and lipid ratios such as TC/HDL-C, TG/HDL-C, LDL-C/HDL-C could be used as an early indicator of COVID-19 mortality. Furthermore, the study revealed that TyG index and TG/HDL-C indices are biochemical markers of COVID-19 severe prognosis.