The Impact of Body Mass Index, Residual Beta Cell Function and Estimated Glucose Disposal Rate on the Development of Double Diabetes and Microvascular Complications in Patients With Type 1 Diabetes Mellitus.

Background The clinical impact of body mass index (BMI), residual beta cell function and estimated glucose disposal rate (eGDR) in the development of double diabetes (DD) and microvascular complications are largely unknown. We aimed to assess whether BMI, residual beta cell function measured by plasma "C" peptide and insulin resistance measured by eGDR have any impact on the development of DD and microvascular complications in patients with type 1 diabetes mellitus (T1DM). Methods It is a cross-sectional observational study involving 113 T1DM patients of more than five years duration who were classified into two groups: normal BMI (18.5-22.9 kg/m2) and overweight/obese group (≥ 23kg/m2) based on Asian BMI classification. Based on their eGDR values, they were grouped into four categories: ≥ 8, 6-7.99, 4-5.99, and < 4 mg/kg/min. The prevalence of DD based on eGDR values was determined. Their BMI and different eGDR categories were compared with the prevalence of diabetic retinopathy and nephropathy and their odds ratio (OR) was calculated. Results The median and interquartile range (IQR) of the eGDR of the overweight/obese group was significantly lower than the normal BMI group (5.3 [3.96-8.15] vs 8.72 [6.50-9.77 mg/kg/min], p < 0.001). The prevalence of DD in the overweight/obese T1DM group and normal BMI group was 75% and 33.3% respectively. The OR of retinopathy and nephropathy in the overweight/obese group was 3.28 (p = 0.007) and 3.01 (p = 0.015) respectively when compared to the normal BMI group. The OR of retinopathy and nephropathy in T1DM patients with eGDR < 4 mg/kg/min was 17.13 (p = 0.001) and 18.5 (p = 0.001) respectively. The lower the eGDR values, the higher the prevalence of retinopathy and nephropathy regardless of HbA1c levels. Conclusion As overweight and obesity are increasingly becoming more prevalent in T1DM, the eGDR will better predict the development of DD and microvascular complications irrespective of HbA1c levels. It is more useful as a variable and easily inducted into routine clinical practice. However, residual beta cell function was not useful in predicting the development of microvascular complications.

Comparison of Novel Biomarkers of Insulin Resistance With Homeostasis Model Assessment of Insulin Resistance, Its Correlation to Metabolic Syndrome in South Indian Population and Proposition of Population Specific Cutoffs for These Indices.

Background The clustering of risk factors of cardiovascular disease (CVD) in individuals has been defined as Metabolic Syndrome (MetS). The major forerunner of all the components of MetS is Insulin Resistance (IR) which is measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and requires the measurement of fasting plasma insulin levels. We attempted to study the performance of lipid-based biochemical markers of IR for the diagnosis of MetS and postulate a population-specific cutoff for these indices in the South Indian population. In this study, we analyzed three lipid-based indices, Triglyceride Glucose index (TyG index), triglyceride: high-Density Lipoprotein (TG:HDL) ratio, and lipid accumulation product (LAP).  Methods This was a cross-sectional study and included apparently healthy individuals presenting to our hospital for routine Master Health Checkup assessment and apparently healthy population residing in Kallindhiri, a village near Madurai. Based on the anthropometric measurements and blood investigations, Body Mass Index (BMI), Waist hip ratio, Waist height ratio, HOMA-IR, TyG index, TG:HDL ratio, and LAP were calculated. The diagnostic efficacy of these indices was compared against the presence of MetS based on the NCEP ATP III criteria. The receiver operating characteristic (ROC) Curve was performed to discriminate decision levels (cutoffs) of serum markers in early diagnosis of metabolic syndrome. The results were considered significant with a p-value less than 0.05. Results We included a total of 192 patients in our study, consisting of 36% (n=70) males and 63% (n=122) females. All the baseline characteristics except height, weight, and HDL cholesterol were comparable between the male and female groups. The values of HOMA-IR, TyG index, TG:HDL ratio, and LAP showed an increasing trend with the BMI. The mean values of HOMA-IR, TyG index, TG:HDL ratio and LAP was significantly higher in patients with MetS than in patients without MetS. Based on the ROC curve plotted for the data, a population-specific cutoff for these indices was computed. Our proposed cutoff for the South Indian population for HOMA-IR is 1.23, for TyG index is 4.65, for TG:HDL ratio is 3.44 in males and 2.6 in females and for LAP is 43.81 Conclusion The cutoffs for the novel indices of insulin resistance which have been previously studied in Caucasian populations cannot be applied to Indian populations due to distinct ethnic characteristics. The diagnostic accuracy of these novel lipid-based biomarkers of Insulin Resistance is better than the biochemical gold standard of HOMA-IR based on the ROC curve. We propose the usage of these population-specific cutoffs in routine clinical practice for early diagnosis of metabolic syndrome.

Epidemiology, Clinical Profile, and Analysis of Risk Factors in COVID Associated Rhino-orbito-cerebral Mucormycosis Patients - An Observational Study.

Aim of Study: To study the clinico-epidemiological profile and identify risk factors for the development of COVID-19-associated mucormycosis (CAM) among the patients treated at our regional mucormycosis center. Materials and Methods: This was a cross-sectional single-centre observational study. All CAM patients admitted to Government Rajaji Hospital, Madurai from April 2021- August 2021 were included in the study. Information regarding clinical features, potential risk factors, diagnostic workup, and comorbid illness was collected. Results: A total of 164 patients of CAM were admitted to our hospital with a mean age of 51.7 years. Out of 164 patients, 12 patients were not covid positive, based on imaging and RT-PCR, however subclinical infection could not be ruled out. Out of the 164 patients studied, 160 patients had diabetes, out of which 66% (n = 105) patients had a previous history of diabetes, and 34% (n = 55) had newly detected diabetes. Most of the patients admitted with mucormycosis had uncontrolled diabetes (94%) and were not on insulin therapy, but were on oral antidiabetic drugs alone. The majority of the patients (68%) have received steroids (IV/oral) during the COVID-19 illness. 74% of these patients were under hospitalization for COVID-19 disease. Only 30% (n = 50) of CAM patients had a history of oxygen therapy and 7% of these patients were treated in ICU during active COVID-19 illness. 59% of patients used cloth masks without adequate hygiene, rest 41% (n = 67) patients reused disposable masks. We also found that 87% of the patients developing mucormycosis had exposure to organic material in the convalescence period of COVID-19 illness. Conclusions: From our study, we found steroid use, poorly controlled diabetes mellitus, reuse of masks, daily steam inhalation, and exposure to organic matter to be more associated with CAM, but oxygen therapy was less associated with CAM. Hence, we could suggest screening for hyperglycemia and daily use of disposable surgical masks to be continued for at least 4 weeks post-COVID-19. It is preferable to continue insulin in titrated doses along with OHA for at least 4 weeks following steroid cessation in the post-COVID-19 period as there is are considerably increased inflammatory cytokine levels in the convalescence phase. Clean environmental hygiene would also help prevent CAM.

The Spectrum of CYP21A2 Gene Mutations from 16 Families of Congenital Adrenal Hyperplasia: Genotype-Phenotype Correlation.

Aim: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of the adrenal steroidogenic pathway. The most common form of CAH is due to 21-hydroxylase deficiency resulting from mutations in CYP21A2 gene. The present study aimed to identify CYP21A2 common gene mutations, phenotype correlation, and to analyze the segregation pattern in CAH patients, parents, and siblings. Materials and Methods: Sixteen families having at least one classic CAH child in each family, a total of 58 subjects were recruited. The presence of six most common gene mutations, namely, Intron 2 (c.293-13A/C>G), c.844G>T (p.Val282Leu), c.1019G>A (p.Arg340His), c.92C>T (p.Pro31Leu), c.955C>T (p.Gln319*), and c.518T>A (p.Ile173Asn) in CYP21A2 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using specific primers. Results: Out of 16 classic CAH females analyzed, salt-wasting (SW) form was present in 12 (75%) and simple virilizing form in four (25%) children. Isolated clitoromegaly was the most common clinical presentation followed by ambiguous genitalia. The most common mutation observed in CAH patient population was Intron 2 (c.293-13A/C>G) (100%) followed by p.Pro31Leu (98%), p.Gln319* (93%), p.Val282Leu (91.4%), and p.Ile173Asn (19%). Although p.Arg340His mutation was not observed in this study. Interestingly, Intron 2 (c.293-13A/C>G) homozygous was observed in 31.3% of the entire study cohort and p.Ile173Asn mutation was found to be associated with SW form. Conclusions: Our results suggested a high prevalence of CYP21A2 gene mutations among CAH patients and heterogeneous mutation spectrum in their families of south Indian cohort. The outcomes afford valuable evidence for premarital and prenatal screening as well as planning suitable programs to prevent the development of CAH in Indian population.