Association of hyperglycaemia at-admission & diabetes mellitus with 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection: A retrospective study

Background & objectives: The association between hyperglycaemia at admission, diabetes mellitus (DM) status and mortality in hospitalized SARS-CoV-2 infected patients is not clear. The purpose of this study was to determine the relationship between DM, at-admission hyperglycaemia and 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection requiring intensive care. Methods: All consecutive moderate-to-severe patients with SARS-CoV-2 infection admitted to the intensive care units (ICUs) over six months were enrolled in this single-centre, retrospective study. The predicators for 28 day mortality were analysed from the independent variables including DM status and hyperglycaemia at-admission. Results: Four hundred and fifty two patients with SARS-CoV-2 were admitted to the ICU, with a mean age of 58.5±13.4 yr, 78.5 per cent being male, HbA1c of 7.2 per cent (6.3-8.8) and 63.7 per cent having DM. Overall, 28 day mortality was 48.9 per cent. In univariate analysis, mortality in diabetes patients was comparable with non-diabetes (47.9 vs. 50.6%, P=0.58), while it was significantly higher in hyperglycaemic group (60.4 vs. 35.8%, P<0.001). In multivariate Cox regression analysis, after adjusting for age, sex and comorbidities, hyperglycaemia at-admission was an independent risk factor of mortality [hazard ratio (HR) 1.45, 95% confidence interval (CI) (1.06-1.99), P<0.05]. Interpretation & conclusions: This study showed that the presence of hyperglycaemia at-admission in critically ill SARS-CoV-2 patients was an independent predictor of 28 day mortality. However, the findings may be susceptible to unmeasured confounding, and more research from prospective studies is required.

Glycemic Control and Long-term Complications in Pediatric Onset Type 1 Diabetes Mellitus: A Single-center Experience from Northern India

Objective: To study glycemic control, mortality and long-termcomplications in children with type 1 diabetes (T1D).Design: Cross-sectional study.Setting: Referral centre at a government teaching hospital.Participants: Patients with T1D with age ≤18 years at onset.Methods: We retrospectively collected demographic data fromcomputer records from 1991 to 2015. Prospective study foroutcomes was conducted between 2012 and 2016.Main outcome measures: Mortality rate, glycosylatedhemoglobin (HbA1c), and microvascular complication rate.Results: The proportion of T1D patients (n=512) <5 years of ageat onset was 18.6% between 1995 and 2004, and 24.2% in2005-2014 (P<0.001). Twenty eight patients had died out of 334whose living status was known (mortality 1.1 per 100 patient-years over 2549 patient-years follow up). Median (range)HbA1c (n=257) was 8.3% (5.1-15.0%). At least one episode ofsevere hypoglycemia (coma/seizure/inability to assist self) hadoccurred in 22.8% patients over two years. Hypertension waspresent in 11.7% patients. Microvascular complications screenin 164 eligible patients [median (range) age 20 (8-45) y andduration of diabetes 9.1 (5-30) y] showed diabetic nephropathy in3.0%, proliferative retinopathy in 3.6% and LDL cholesterol >100mg/dL in 34% patients.Conclusion: The mortality rate and prevalence of hypertensionwere high, given the short duration of diabetes of the patients.The proportion of patients with age ≤5 years at onset of diabeteshas increased at our center.

High direct costs of medical care in patients with Type 1 diabetes attending a referral clinic in a government-funded hospital in Northern India.

Background. There is little information regarding costs of managing type 1 diabetes mellitus (T1DM) from low- and middle-income countries. We estimated direct costs of T1DM in patients attending a referral diabetes clinic in a governmentfunded hospital in northern India. Methods. We prospectively enrolled 88 consecutive T1DM patients (mean [SD] age 15.3 [8] years) with age at onset <18 years presenting to the endocrine clinic of our institution. Data on direct costs were collected for 12 months—6 months retrospectively followed by 6 months prospectively. Results. Patients belonged predominantly (77%) to the middle socioeconomic strata (SES); 81% had no access to government subsidy or health insurance. The mean direct cost per patient-year of T1DM was `27 915 (inter-quartile range [IQR] `19 852–32 856), which was 18.6% (7.1%–30.1%) of the total family income. A greater proportion of income was spent by families of lower compared to middle SES (32.6% v. 6.6%, p<0.001). The mean out-of-pocket payment for diabetes care ranged from 2% to 100% (mean 87%) of the total costs. The largest expenditure was on home blood glucose monitoring (40%) and insulin (39.5%). On multivariate analysis, total direct cost was associated with annual family income (β=0.223, p=0.033), frequency of home blood glucose monitoring (β=0.249, p=0.016) and use of analogue insulin (β=0.225, p=0.016). Conclusions. Direct costs of T1DM were high; in proportion to their income the costs were greater in the lower SES. The largest expenditure was on home blood glucose monitoring and insulin. Support for insulin and glucose testing strips for T1DM care is urgently required. Natl Med J India 2016;29:64–7

Prevalence of Graves’ ophthalmopathy in patients with Graves’ disease presenting to a referral centre in north India.

Background & objectives: The prevalence of Graves’ ophthalmopathy (GO) varies widely in different ethnic groups. Indians have been reported to have a lower prevalence of Graves’ ophthalmopathy as compared to Caucasians of European origin, but data are sparse and inconclusive. We studied the prevalence, clinical features and association of GO in Indian patients with Graves’ disease attending a referral centre in north India. Methods: A prospective study was conducted on 235 consecutive newly referred north Indian patients with Graves’ disease presenting to a tertiary care centre in north India. All patients underwent a comprehensive ophthalmological examination as per the European Group on Graves’ Orbitopathy (EUGOGO) recommendations. Results: GO was diagnosed in 65 patients (prevalence 28%; 95% confidence interval 22-33%). The prevalence was similar in males (28%) and females (27%). It was mild in 83 per cent, moderate-severe in 15 per cent and sight-threatening in only 2 per cent of cases. Ophthalmopathy was clinically active in only two (3%) cases. Upper eyelid retraction was the most common manifestation (83%), followed by exophthalmos (75%). Extra-ocular muscle involvement (5%) and optic nerve dysfunction (2%) were uncommon. The risk of GO was 3.9- fold (95% confidence interval 1.1-13.6) higher in smokers compared to non-smokers. However, severity of disease in smokers was similar to non-smokers. On multivariate logistic regression analysis, GO was associated only with high thyrotropin receptor antibody titres and current smoking. Interpretation & conclusions: Among north Indian patients with GD studied at a referral center, the prevalence of GO was similar to Caucasians of European descent, but clinically active and severe ophthalmopathy was uncommon. More studies are needed to confirm these findings.

Intensive glycaemic control in type 2 diabetes mellitus: Does it improve cardiovascular outcomes.

With growing urbanization and economic development, there is a rapid increase in the incidence of type 2 diabetes mellitus (T2DM) in India. T2DM is associated with 2–4 times higher risk for cardiovascular disease (CVD), including coronary artery disease, stroke and peripheral vascular disease. Several studies have shown the benefit of intensive glycaemic control in reducing the frequency of diabetic microvascular complications such as retinopathy and nephropathy. Results of long term follow up of patients with diabetes, who were enrolled in earlier trials, have shown that initial intensive glycaemic control led to a reduction in CVD outcomes when compared with standard therapy. However, it is unclear if intensive glycaemic control, aiming to reduce haemoglobin A1c to levels even lower than the current goal of <7%, will similarly lead to reduction in the rates of CVD. Recently, the results of 3 large, randomized controlled trials have been published, which suggest that in established T2DM with previous CVD or high risk of CVD, the benefits of intensive glycaemic control when compared with conventional good control, are minimal with regards to reduction of cardiovascular outcomes. Intensive therapy increases the risk of side-effects such as severe hypoglycaemia and weight gain. The implementation of such a therapy, with rigorous attention to frequent monitoring of blood glucose and visits to the physician, is not likely to be possible on a large scale, especially in a developing country such as India. The aim of management of patients with established T2DM should be to achieve the goal of good glycaemic control (haemoglobin A1c <7%), with avoidance of hypoglycaemia. It is equally, if not more important, to control other risk factors of CVD by paying greater attention to lifestyle measures (weight loss if overweight or obese, regular exercise, cessation of smoking), rigorous control of blood pressure (<130/80 mmHg) and low density lipoprotein (LDL) cholesterol (<100 mg/dl or <70 mg/dl if already diagnosed with CVD) and the prophylactic use of low dose aspirin as per current recommendations. A multifactorial approach targeting multiple cardiovascular risk factors is likely to be most effective in reducing CVD outcomes in T2DM.

Insulin therapy for patients with type 1 diabetes.

The incidence of type 1 diabetes is increasing world wide, especially in younger children. Unfortunately, there is little information on the incidence of type 1 diabetes or its management from India. Recent studies have emphasized the importance of strict glycemic control in the prevention and delay of chronic microvascular complications of diabetes mellitus. This has lead to increasing efforts in devising means of physiological insulin delivery, in which basal insulin and meal related boluses of insulin are separately given and insulin doses are appropriately altered based on frequent blood glucose testing, meal size and exercise. Newer insulin analogues, which better mimic basal and meal related increments of insulin secretion, have been marketed. Regimes for physiological insulin delivery, such as multiple subcutaneous insulin injections and continuous subcutaneous insulin infusion are becoming increasingly popular. However, the high frequency of hypoglycemia is an important constraint to achieving normal glycemic control. In developing countries such as India, other obstacles include the high cost of insulin and blood glucose monitoring strips, social barriers to accepting insulin injections and lack of trained teams for management of type 1 diabetes.

HFE, hepcidin and ferroportin gene mutations are not present in Indian patients with primary haemochromatosis.

BACKGROUND: Primary haemochromatosis is characterized by iron overload in the body tissues. It is common in populations of northern European descent. In such populations, 85%-90% of patients with this disease have a C282Y mutation in the HFE gene. In India, the disease is uncommon and the genetic defects associated with it are unknown. We therefore looked for mutations in the HFE and other genes involved in iron metabolism in Indian patients with primary haemochromatosis. METHODS: Five patients (including a brother-sister pair) with primary haemochromatosis diagnosed on clinical, biochemical and histological findings were studied. Genomic DNA was analysed by sequencing for the presence of mutations in all the 6 exons of the HFE gene and for previously described mutations in genes encoding hepcidin antimicrobial peptide and ferroportin. RESULTS: No patient had the C282Y mutation. One had homozygous H63D mutation. No other mutation was found in any HFE exon. Two previously reported splice site mutations in the HFE gene (IVS3 + 1 G/T and IVS5+1 G/A) were not detected. Four of the 5 patients had an HFE splice site mutation (IVS2 + 4 T/C; homozygous 2, heterozygous 2); however, this change was as frequent in 29 healthy subjects (homozygous 9, heterozygous 7), and was present in only 1 of the sibling pair patients, indicating that this represented a polymorphism. No patient had any of the previously described mutations in the genes for hepcidin and ferroportin. CONCLUSION: Our patients with primary haemochromatosis lacked mutations in the HFE, hepcidin and ferroportin genes. Further genetic analysis may help identify novel mutations responsible for primary haemochromatosis in these patients.