Low FT3 is an independent marker of disease severity in patients hospitalized for COVID-19.

AIM: To study the prevalence of thyroid dysfunction and its association with disease severity in hospitalized patients of coronavirus disease-19 (COVID-19). METHODS: In this retrospective cohort study, thyroid function tests (TFT) of 236 hospitalized patients of COVID-19 along with demographic, comorbid, clinical, biochemical and disease severity records were analysed. Patients were divided into previous euthyroid or hypothyroid status to observe the effect of prior hypothyroidism on the severity of COVID-19. RESULTS: TFT abnormalities were common. Low free T3 (FT3), high thyroid-stimulating hormone (TSH) and low TSH were seen in 56 (23.7%), 15 (6.4%) and 9 (3.8%) patients, respectively. The median levels of TSH (2.06 vs 1.26 mIU/mL, P = 0.001) and FT3 (2.94 vs 2.47 pg/mL, P < 0.001) were significantly lower in severe disease. Previous hypothyroid status (n = 43) was associated with older age, higher frequency of comorbidities, higher FT4 and lower FT3. TFT did not correlate with markers of inflammation (except lactate dehydrogenase); however, FT3 and TSH negatively correlated with outcome severity score and duration of hospital stay. Cox regression analysis showed that low FT3 was associated with severe COVID-19 (P = 0.032, HR 0.302; CI 0.101-0.904), irrespective of prior hypothyroidism. CONCLUSIONS: Functional thyroid abnormalities (low FT3 and low TSH) are frequently seen in hospitalized patients of COVID-19. Although these abnormalities did not correlate with markers of inflammation, this study shows that low FT3 at admission independently predicts the severity of COVID-19.

Type 2 diabetes and bone fragility- An under-recognized association.

BACKGROUND AND AIMS: Diabetes and osteoporosis are common chronic disorders with growing prevalence in the aging population. Skeletal fragility secondary to diabetes increases the risk of fractures and is underestimated by currently available diagnostic tools like fracture risk assessment (FRAX) and dual-energy X-ray absorptiometry (DXA). In this narrative review we describe the relationship and pathophysiology of skeletal fragility and fractures in Type 2 diabetes (T2DM), effect of glucose lowering medications on bone metabolism and the approach to diagnosing and managing osteoporosis and bone fragility in people with diabetes (PWD). METHODS: A literature search was conducted on PubMed for articles in English that focused on T2DM and osteoporosis or bone/skeletal fragility. Articles considered to be of direct clinical relevance to physicians practicing diabetes were included. RESULTS: T2DM is associated with skeletal fragility secondary to compromised bone remodeling and bone turnover. Long duration, poor glycemic control, presence of chronic complications, impaired muscle function, and anti-diabetic medications like thiazolidinediones (TZD) are risk factors for fractures among PWD. Conventional diagnostic tools like DXA and FRAX tool underestimate fracture risk in diabetes. Presence of diabetes does not alter response to anti-osteoporotic treatment in post-menopausal women. CONCLUSION: Estimation of fragility fracture risk should be included in standard of care for T2DM along with screening for traditional complications. Physicians should proactively screen for and manage osteoporosis in people with diabetes. It is important to consider effects on bone health when selecting glucose lowering agents in people at risk for fragility fractures.

Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19.

Vitamin D deficiency (VDD) owing to its immunomodulatory effects is believed to influence outcomes in COVID-19. We conducted a prospective, observational study of patients, hospitalized with COVID-19. Serum 25-OHD level < 20 ng/mL was considered VDD. Patients were classified as having mild and severe disease on basis of the WHO ordinal scale for clinical improvement (OSCI). Of the 410 patients recruited, patients with VDD (197,48.2%) were significantly younger and had lesser comorbidities. The levels of PTH were significantly higher in the VDD group (63.5 ± 54.4 vs. 47.5 ± 42.9 pg/mL). The proportion of severe cases (13.2% vs.14.6%), mortality (2% vs. 5.2%), oxygen requirement (34.5% vs.43.4%), ICU admission (14.7% vs.19.8%) was not significantly different between patients with or without VDD. There was no significant correlation between serum 25-OHD levels and inflammatory markers studied. Serum parathormone levels correlated with D-dimer (r 0.117, p- 0.019), ferritin (r 0.132, p-0.010), and LDH (r 0.124, p-0.018). Amongst VDD patients, 128(64.9%) were treated with oral cholecalciferol (median dose of 60,000 IU). The proportion of severe cases, oxygen, or ICU admission was not significantly different in the treated vs. untreated group. In conclusion, serum 25-OHD levels at admission did not correlate with inflammatory markers, clinical outcomes, or mortality in hospitalized COVID-19 patients. Treatment of VDD with cholecalciferol did not make any difference to the outcomes.

High prevalence of diabetes and other comorbidities in hospitalized patients with COVID-19 in Delhi, India, and their association with outcomes.

BACKGROUND AND AIMS: To study the prevalence and impact of diabetes mellitus and other comorbidities among hospitalized patients with COVID-19. METHODS: In a prospective, observational study including consecutive adults hospitalized with COVID-19, clinical outcomes and inflammatory markers were compared in those with and without diabetes. Participants were classified as having mild or severe COVID-19 disease using the WHO ordinal scale. RESULTS: 401 patients (125 females) with median age of 54 years (range 19-92) were evaluated. Of them 189 (47.1%) had pre-existing diabetes and21 (5.2%) had new-onset hyperglycaemia. Overall, 344 (85.8%) and 57 (14.2%) cases had mild and severe COVID-19 disease respectively. The group with diabetes had a higher proportion of severe cases (20.1% vs 9%, p-0.002), mortality (6.3 vs 1.4%, p-0.015), ICU admission (24.3 vs 12.3%, p-0.002), and oxygen requirement (53.4 vs 28.3%, p < 0.001). Baseline Hba1c (n = 331) correlated significantly with outcome severity scores (r 0.136, p-0.013) and 12/15 (80%) of those who succumbed had diabetes. Hypertension, coronary artery disease, and chronic kidney disease were present in 164 (40.9%), 35 (8.7%) and 12 (2.99%) patients respectively. Hypertension was associated with a higher proportion of severe cases, mortality, ICU admission and oxygen administration. CONCLUSIONS: We report a high prevalence of diabetes in a hospitalized COVID-19 population. Patients with diabetes or hypertension had more severe disease and greater mortality.

Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial).

AIMS/HYPOTHESIS: Liraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). METHODS: Effect of dulaglutide on liver fat (D-LIFT) was a 24 week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (n = 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24 weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24 weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes. RESULTS: Eighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of -3.5% (95% CI -6.6, -0.4; p = 0.025) and relative change of -26.4% (-44.2, -8.6; p = 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference -13.1 U/l [95% CI -24.4, -1.8]; p = 0.025) and non-significant reductions in aspartate aminotransferase (AST) (-9.3 U/l [-19.5, 1.0]; p = 0.075) and alanine aminotransferase (ALT) levels (-13.1 U/l [-24.4, 2.5]; p = 0.10). Absolute changes in PFC (-1.4% [-3.2, 0.3]; p = 0.106) and LSM (-1.31 kPa [-2.99, 0.37]; p = 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events. CONCLUSIONS/INTERPRETATION: When included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03590626 FUNDING: The current study was supported by an investigator-initiated study grant from Medanta-The Medicity's departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India. Graphical abstract.

Judicious use of DXA-BMD in assessing fracture risk by using clinical risk factors in the Indian population.

FRAX scores were significantly higher in patients admitted with fragility fractures than controls and can be useful in choosing the right patients for bone density testing, thus using of an expensive test judiciously. PURPOSE: This study was planned to compare the FRAX scores for the risk for major osteoporotic fracture (FRAX-MOF) and hip fracture (FRAX-HF) in patients with fragility fractures (cases) and those admitted for other indications (controls) in the orthopedic ward in our institute. METHODS: Historical and anthropometric data were prospectively recorded from 500 consecutive patients admitted in the orthopedic ward in in Medanta, the Medicity, Gurgaon, India. The receiver operating characteristic (ROC) curves were constructed for FRAX-MOF and FRAX-HF and the area under the curve (AUC) was calculated between cases and controls. RESULTS: The FRAX-MOF was significantly high in cases as compared to controls (7.34 ± 4.41 versus 5.64 ± 4.3; p = 0.001). The FRAX-HF was also significantly high in cases as compared to controls (2.95 ± 3.13 versus 1.67 ± 2.21; p < 0.001). The areas under the curves were 0.627 for FRAX-MOF and 0.654 for FRAX-HF. For FRAX-MOF, a cutoff of 2 has a 90% sensitivity, but only 15% specificity; whereas a cutoff of 10.5 had a specificity of 90% to differentiate those with and without fractures, but only 23% sensitivity. For FRAX-HF, a cutoff 0.3 had about 90% sensitivity and 20% specificity, whereas a cutoff of 3.5 had 90% specificity and 25% specificity to differentiate cases and controls. CONCLUSIONS: This study compared the FRAX-MOF and FRAX-HF in patients with and without fragility fractures and derived cutoffs for practical clinical use of FRAX-MOF and FRAX-HF to optimize the use of DXA-BMD.

Cutaneous mucormycosis as a presenting feature of type 1 diabetes in a boy - case report and review of the literature.

BACKGROUND: Mucormycosis is a potentially fatal complication of diabetes. The rhino-orbito-cerebral form is the most common presentation, however, rarely other types can also be seen. CASE PRESENTATION: We describe the case of a 4½ -year-old boy not previously known to be a diabetic who presented to the plastic surgery department for gangrene of the left middle finger with surrounding erythema and induration. After the diagnosis of diabetes and initial treatment, pus from the wound showed broad aseptate hyphae suggestive of mucormycosis which was further confirmed on culture. Aggressive surgical debridement including amputation, antifungal treatment and glycemic control achieved a complete cure. CONCLUSIONS: Cutaneous mucormycosis is a rare complication of type 1 diabetes mellitus and can even be seen at the onset of diabetes. High index of suspicion, timely antifungal treatment and aggressive surgical debridement usually lead to recovery in the localized form of the disease.

Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review

SUMMARY Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

Effect of oral versus intramuscular Vitamin D replacement in apparently healthy adults with Vitamin D deficiency.

CONTEXT: A number of controversies exist regarding appropriate treatment strategy for Vitamin D deficiency. AIMS: The aim of this study was to investigate the efficacy of equivalent doses of oral cholecalciferol (60,000 IU weekly for 5 weeks) versus intramuscular (IM) cholecalciferol (300,000 IU) in correcting Vitamin D deficiency in apparently healthy volunteers working in a hospital. SETTINGS AND DESIGN: Prospective randomized open-label single institution study. SUBJECTS AND METHODS: This study enrolled 40 apparently healthy adults with Vitamin D deficiency into 2 arms. The oral cholecalciferol group (n = 20) received oral cholecalciferol 60,000 IU weekly for 5 weeks while the IM cholecalciferol group (n = 20) received a single injection of cholecalciferol 300,000 IU. The main outcome measure was serum 25-hydroxyvitamin D (25OHD) levels at baseline, 6 and 12 weeks after the intervention. STATISTICAL ANALYSIS USED: Differences in serum 25OHD and other biochemical parameters at baseline and follow-up were analyzed using general linear model. RESULTS: Mean 25OHD level at baseline was 5.99 ± 1.07 ng/mL and 7.40 ± 1.13 ng/mL (P = 0.332) in the oral cholecalciferol and IM cholecalciferol group, respectively. In the oral cholecalciferol group, serum 25OHD level was 20.20 ± 1.65 ng/mL at 6 weeks and 16.66 ± 1.36 ng/mL at 12 weeks. The corresponding serum 25OHD levels in the IM cholecalciferol group were 20.74 ± 1.81 ng/mL and 25.46 ± 1.37 ng/mL at 6 and 12 weeks, respectively. At 12 weeks, the mean 25OHD levels in IM cholecalciferol group was higher as compared to the oral cholecalciferol group (25.46 ± 1.37 vs. 16.66 ± 1.36 ng/mL; P < 0.001). CONCLUSIONS: Both oral and IM routes are effective for the treatment of Vitamin D deficiency. 25-hydroxyvitamin D levels in the IM cholecalciferol group showed a sustained increase from baseline.

Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review.

Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

Childhood and Youth Onset Diabetes: A Single Centre Experience.

OBJECTIVES: To identify proportion of various types of diabetes and differences between type 1 and type 2 diabetes in patients with youth onset diabetes (onset below 25 completed years of age). In addition, concurrent autoimmune diseases in type 1 diabetes were studied in a subset of patients. METHODS: A total of 577 patients (192 girls) with diabetes onset at median age of 14 y (range 1 mo-25 y) with median duration of 1 y (range day of diagnosis- 43 y) were included. Clinical details, investigations and complications were recorded in a proforma. Diabetes was classified using clinical criteria supported by laboratory tests of C peptide and anti GAD-65 antibody in a subset of patients. RESULTS: Type 1 diabetes accounted for 368/421 (87.4 %) patients with age of onset <18 y and 99/156 (63.5 %) of patients with onset between 19 and 25 y of age. Proportion of type 2 diabetes was 36/421 (8.5 %) and 41/156 (26.2 %) in these two groups. Older age at onset, diabetes in one or both parents, absence of ketosis /weight loss and presence of acanthosis were significant predictors of type 2 diabetes. Hypothyroidism (TSH >10) and biopsy proven celiac disease was found in 11.6 and 9.7 % of type 1 diabetes patients respectively. CONCLUSIONS: Type 1 diabetes is the most common type of diabetes in youth, however, a significant proportion of youth have type 2 diabetes. In these patients a combination of clinical factors, biochemical parameters and course over few months helps to guide the diagnosis.