An Observational Study of the Physical and Biochemical Complications and Socioeconomic Status of Type 1 Diabetic Patients in West Bengal, India: A 25-year Follow-up Report of 224 Patients.

BACKGROUND: Limited information is available on the total profile of type 1 diabetes mellitus patients in India. The present study has been undertaken, therefore, in search of socioeconomic status, glycaemic status and the state of complications of the type 1 diabetics attending the diabetic clinic run by Calcutta Diabetes and Endocrine Foundation (CDEF), Kolkata. OBJECTIVES: (1) To obtain the glycemic, socioeconomic, and complications status of type 1 diabetic patients; (2) to see any change of the abovementioned parameters in this follow-up period of 25 years; (3) to take necessary action to improve the quality of care and the health condition of the type 1 diabetics attending the clinic. STUDY DESIGN AND SETTING: A longitudinal observational study. A total of 265 patients were recruited for the study, having been diagnosed or seen within 1 year of diagnosis of type 1 diabetes at the Diabetic Clinic of CDEF. A total of 41 patients were excluded from the study for different reasons, and 224 patients were finally selected. These 224 patients were classified into five separate cohorts according to their first attendance in the diabetes clinic: 1996-2000 (I), 2001-2005 (II), 2006-2010 (III), 2011-2015 (IV), and 2016-2020 (V). Baseline and socioeconomic (based on education and occupational status) data was obtained at the first visit, and mean biochemical parameters were taken from multiple visits. Complications and mortality rates were calculated against the duration of the disease at the end of the study. RESULTS: Gradual improvement of glycemic status was noted when groups I and V were compared. Delayed development of complications and comparatively long life were also observed. CONCLUSION: Several methods of improvement of clinical disease management, including continuous diabetes education with proper training, can improve diabetes care, leading to delays in the development of diabetic complications and ensuring longer as well as healthier life in type 1 diabetes. The development of socioeconomic status might have played some role.

An Observational Study on the Mortality Pattern of Type 1 Diabetic Patients in West Bengal, India: A 22 Years' Follow Up Report of 212 Patients.

Information on the total profile of type 1 diabetes mellitus (T1DM) patients in India, is limited,as type1 diabetes is not that common in India. This study,tried to search of mortality pattern of the type 1 diabetics attending the diabetic clinic run by the Calcutta Diabetes and Endocrine Foundation at Kolkata which has a special diabetes care program for the type 1 diabetics. MATERIAL: 264, type 1 diabetics attending our clinic were considered for the study. The patients registered in the clinic since April 1996 and had at least one or more follow up visits per year have been included in the study. Follow-up up to 31st March, 2019 have been determined as selection criteria. Out of 264, 212 patients satisfied the criteria and therefore have been included in the study, others excluded. OBSERVATION: Out of 212 patients,22 (10.38%) patients expired during the study period. 8 (36.36%) of them were males and 14 (63.64%) were females. The age of the expired patients at death varied from 5 to 73 years. 3 (13,64%) patients died within 20 years of age,14 (63.64%) between 21-40 years, 2 (9.09%) between 41 - 60 years and 3 (13.63%) were above 60 years. Cause of death for maximum number of patients was Chronic Kidney Disease (CKD) (45.45%), followed by Diabetic Ketoacidosis (DKA, 18.18%), 3.63% died of Coronary Artery Disease, 9.09% of infections (pneumonia, encephalitis). Accidental and psycho-social reasons were present in 13.63%. CONCLUSION: In this observational study, the total number of death observed was 22 out of 212 type 1 diabetic patients in this 22 years' period. CKD is the leading cause of death in this cohort, followed by DKA, Infection, and Coronary Artery Disease. Infection and DKA was found in the poor socio economic group. Some patients died of accident and other psycho social problem in the family. A regular communication with the patients made a lot of positive influence in our patients.

A Menace without Specific Feature - Scrub Typhus a Reemerging Disease.

INTRODUCTION: Scrub typhus is a re-emerging infectious disease. Though considered as disease of rural areas, this disease has been urbanized and the prevalence has broadened further. Disease has been reported with increasing frequency from various parts of India and has resurgence in north east. It is a disease with multi organ involvement, with or without characteristic eschar and early detection and initial specific treatment is important. MATERIAL: An observational hospital-based study in patients >18years admitted to a tertiary care center in eastern India. Scrub typhus was diagnosed on basis of symptoms with or without eschar and Scrub IgM. Treated with doxycycline (azithromycin in 3 pregnant patients) & clinical course was monitored. An appropriate correlation measure, based on the natures of the variable under study, (e.g.: rank correlation / Pearson correlation/ point biserial correlation) was estimated and subsequently tested at alpha =0.05 level of significance. A p value <0.05 was taken as significant. OBSERVATIONS: A total of 105 patients of scrub typhus were included in present study. It had 66%male and 39% female with the most common age group being 46-60 years. Eschar was found in 33% patients. Neurological manifestation was found in 18% of the patients. Hyponatremia and raised liver enzymes were significantly noticed. 9% patients had Acute respiratory distress syndrome. 4% patients died because of multiorgan dysfunction. Three pregnant patients included in study were treated with azithromycin showed good response and pregnancy outcome was uneventful. CONCLUSIONS: Scrub typhus is no longer a disease of rural India. Physician should have strong suspicion and needs early attempt to diagnose and treat as mostly the disease is featureless and can be treated easily, but delay in starting treatment raises chances of severe complications like encephalitis, ARDS, Macrophage Activation Syndrome. Disease mostly responded with Azithromycin, Doxycycline.

An Observational Study on the Mortality Pattern of Type 1 Diabetic Patients in West Bengal, India: A 22 Years' Follow Up Report of 212 Patients.

BACKGROUND: Limited information is available on the total profile of type 1 diabetes mellitus (T1DM) patients in India as type 1 diabetes is not common in India. The present study has been undertaken therefore, in search of mortality pattern of the type 1 diabetics attending the diabetic clinic run by the Calcutta Diabetes and Endocrine Foundation at Kolkata which has a special diabetes care program for the type 1 diabetics. OBJECTIVES: • To obtain the mortality rate of type 1 diabetes in India and to compare it with overall Indian mortality. • To identify the role of different complications of diabetes responsible for the death and thereby, getting a mortality pattern in type 1 diabetes. • To take necessary action for prevention of the complication(s), mainly responsible for the death Study Design and settings: Longitudinal Observational Study: A number of 264 type 1 diabetics attending our clinic were considered for the study. The patients registered in the clinic since April 1996 and had at least one or more follow up visits per year have been included in the study. Follow-up up to 31st March, 2019 have been determined as selection criteria. Out of 264, 212 patients satisfied the criteria and therefore have been included in the study. METHODS OF STUDY: Age, sex, height, weight, educational qualifications, profession, annual family income and number of family members of each patient was recorded in the first visit. Age and year of detection of diabetes was also recorded. Fasting and Post Prandial plasma glucose level, insulin type and dose, daily dietary habit, presence of diabetic complications, i.e. Retinopathy Neuropathy, Nephropathy, Coronary Artery Disease. Life Style and diabetic education status were assessed during first visit and also in successive visits. An average value for each of the above parameters was calculated for every patient and recorded to explain their individual status. Mortality data was collected from the patients expired during this period. RESULTS: 22 (10.38%) out of 212 patients were expired during the study period. 8 (36.36%) of them were males and 14 (63.64%) were females. The age of the expired patients at death varied from 5 to 73 years. 3 ( 13,64% ) patients died within 20 years of age,14 (63.64%) between 21-40 years, 2 ( 9.09% ) between 41 - 60 years and 3 ( 13.63% ) were above 60 years. Chronic Kidney Disease (CKD) was the cause of death for maximum number of patients (45.45%) followed by Diabetic Ketoacidosis (DKA, 18.18%),!3.63% died of Coronary Artery Disease, 9.09% of infections (pneumonia, encephalitis). Accidental and psycho-social reasons were present in 13.63%. CONCLUSION: In this observational study, the total number of death observed was 22 out of 212 type 1 diabetic patients in this 22 years' period.CKD is the leading cause of death in this cohort, followed by DKA, Infection, and Coronary Artery Disease. Infection and DKA was found in the poor socio economic group. Some patients died of accident and other psycho social problem in the family. A regular communication with the patients made a lot of positive influence in our patients.

Cross-sectional Study on Vitamin D Status in CKD Patients.

BACKGROUND: Chronic Kidney Disease (CKD) is defined as a disease characterized by alterations in either kidney structure or function or both for a minimum of 3 months duration. New evidences have established new paradigm in the management of CKD patients having Vitamin D deficiency. It appears in some studies that adequate replacement of Vitamin D in deficient population can reduce premature mortality and morbidity in CKD population. AIMS AND OBJECTIVES: This cross-sectional study is designed "To assess Vitamin D status in CKD patients and to correlate Vitamin D status with eGFR. METHODOLOGY: A retrospective cross sectional study on 100 cases of Chronic Kidney Disease patients and matched control subjects in a tertiary care hospital of Eastern India. eGFR was calculated using MDRD-EPI study equation. Vitamin D status was measured using 25(OH) vitamin D levels. Correlation was calculated by Pearson correlation analysis. RESULTS: Among 100 cases, 56 were male and 44 were female. Among 100 control, 53 were female and 47 were male. Among the cases, the mean eGFR was 25.15 ± 11.89. Among the control, the mean eGFR was 87.22 ± 17.82. Among the cases, the mean Vitamin D (Vit D) was 22.57 ± 9.76. Among the control, the mean Vit D was 35.24 ± 10.18. Among the cases, in non-dialysis patients the mean Vit D was 25.66 ± 8.54 and in dialysis patients the mean Vit D was 10.94 ± 2.65. Among the cases, 38 patients had Vit D deficiency (<20), 44 patients had Vit D insufficiency (20-30) and 18 patients had normal Vit D (>30). The positive correlation was found between eGFR and vitamin D level and that was statistically significant. CONCLUSION: Both deficiency and insufficiency of Vitamin D were higher in CKD patients compared to control. Vitamin-D deficiency was more pronounced in advanced stages of CKD. eGFR was strongly associated with serum vitamin-D level.

Socio-demographic and Clinico-Epidemiological Study of Scrub Typhus in Two Tertiary Care Hospitals of Kolkata.

Background and Aims: Scrub typhus is the commonest of the rickettsial diseases in India and is difficult to diagnose. Untreated cases have fatality rates of 30-45%. Eschar is present in 7-97% cases. Pneumonia and acute respiratory distress syndrome (ARDS) are frequent complications. Serum immunoglobulin M capture ELISA is the most sensitive test. Doxycycline is the drug of choice. Our objectives were to study the socio-demographic and clinic-epidemiological profiles of scrub typhus cases in two tertiary care hospitals in Kolkata, India. This was the first study of scrub typhus in Southern West Bengal and its neighboring areas. . Methods: Study was conducted over 16 months and all fever cases of Tropical Medicine / Medicine outpatients' clinics were evaluated. Results: Fourteen cases were diagnosed. 78.6% were from rural areas and 35.7% were farmers. Headache and fever were the commonest presenting complaints while eschar was found in only 21.4%. Serum IgM scrub typhus antibody was positive in all cases . Conclusion: Scrub typhus should be a differential diagnosis in acute febrile illness cases, as early diagnosis and therapy prevents complications.

Excretion kinetics of 13C-urea breath test: influences of endogenous CO2 production and dose recovery on the diagnostic accuracy of Helicobacter pylori infection.

We report for the first time the excretion kinetics of the percentage dose of (13)C recovered/h ((13)C-PDR %/h) and cumulative PDR, i.e. c-PDR (%) to accomplish the highest diagnostic accuracy of the (13)C-urea breath test ((13)C-UBT) for the detection of Helicobacter pylori infection without any risk of diagnostic errors using an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method. An optimal diagnostic cut-off point for the presence of H. pylori infection was determined to be c-PDR (%) = 1.47 % at 60 min, using the receiver operating characteristic curve (ROC) analysis to overcome the "grey zone" containing false-positive and false-negative results of the (13)C-UBT. The present (13)C-UBT exhibited 100 % diagnostic sensitivity (true-positive rate) and 100 % specificity (true-negative rate) with an accuracy of 100 % compared with invasive endoscopy and biopsy tests. Our c-PDR (%) methodology also manifested both diagnostic positive and negative predictive values of 100 %, demonstrating excellent diagnostic accuracy. We also observed that the effect of endogenous CO2 production related to basal metabolic rates in individuals was statistically insignificant (p = 0.78) on the diagnostic accuracy. However, the presence of H. pylori infection was indicated by the profound effect of urea hydrolysis rate (UHR). Our findings suggest that the current c-PDR (%) is a valid and sufficiently robust novel approach for an accurate, specific, fast and noninvasive diagnosis of H. pylori infection, which could routinely be used for large-scale screening purposes and diagnostic assessment, i.e. for early detection and follow-up of patients.

Isotope-specific breath analysis to track the end-stage renal disease during hemodialysis.

The underlying mechanisms towards the progression of end-stage renal disease (ESRD) in chronic kidney disease (CKD) are poorly understood and it still remains a major clinical stumbling block for early detection of CKD. Most patients with CKD pass through ESRD with the necessity of frequent hemodialysis (HD) treatment. At present, plasma urea and creatinine levels are examined in most CKD patients to monitor their health status after dialysis. But it is impossible to get immediate feedback on the patients' health as the conventional tests involve the collection of blood samples, laboratory processing for a prolonged period of time and, finally, analysis of those samples. However, the test results are very important in deciding the treatment plan for those ESRD patients. Here, we show that the enzymatic activity of carbonic anhydrase in erythrocytes is distinctly altered in ESRD subjects under HD. This, in turn, leads to the isotopic enrichments of oxygen-18 (18O) and carbon-13 (13C) of CO2 during respiration in HD treatment. High-resolution cavity-enhanced absorption spectroscopic measurements show that 18O and 13C-isotopic fractionations of breath CO2 are correlated with Kt/V values, suggesting a novel unifying strategy for ESRD patients that can be used as an isotope-specific methodology for non-invasive assessment of dialysis adequacy and hence 12C18O16O and 13C16O16O could be used as novel markers for tracking the physiological parameters of ESRD individuals. Our findings suggest that the monitoring of 18O and 13C isotopes of breath CO2 may facilitate the proper management of advanced CKD patients. The primary advantage of this isotopic breath test is that it may reduce the valuable time lag between the completion of dialysis and obtaining the clinical report on the status of patients' health.

13C isotopic abundances in natural nutrients: a newly formulated test meal for non-invasive diagnosis of type 2 diabetes.

A new method to replace commercially prepared 13C-labelled glucose with naturally available 13C-enriched substrates could result in promotion of the clinical applicability of the isotopic breath test for detection of type 2 diabetes (T2D). Variation of the carbon-13 isotope in human breath depends on the 13C enrichment in the diet taken by subjects. Here, we formulated a new test meal comprising naturally available 13C-enriched foods and subsequently administered it to non-diabetic control (NDC) subjects and those with T2D. We found that the new test meal-derived 13C enrichment of breath CO2 was significantly lower in T2D compared with NDC. Furthermore, from our observations T2D exhibited higher isotopic enrichment of oxygen-18 (18O) in breath CO2 compared with NDC following ingestion of the new meal. We determined the optimal diagnostic cut-off values of 13C (i.e. δ 13C‰ = 7.5‰) and 18O (i.e. Î´ 18O‰ = 3.5‰) isotopes in breath CO2 for precise classification of T2D and NDC. Our new method involving the administration of naturally 13C-abundant nutrients showed a typical diagnostic sensitivity and specificity of about 95%, suggesting a valid and potentially robust global method devoid of any synthetically manufactured commercial 13C-enriched glucose which thus may serve as an alternative diagnostic tool for routine clinical applications.

Targeting erythrocyte carbonic anhydrase and 18O-isotope of breath CO2 for sorting out type 1 and type 2 diabetes.

The inability to envisage the acute onset and progression of type 1 diabetes (T1D) has been a major clinical stumbling block and an important area of biomedical research over the last few decades. Therefore there is a pressing need to develop a new and an effective strategy for early detection of T1D and to precisely distinguish T1D from type 2 diabetes (T2D). Here we describe the precise role of the enzymatic activity of carbonic anhydrase (CA) in erythrocytes in the pathogenesis of T1D and T2D. We show that CA activities are markedly altered during metabolism of T1D and T2D and this facilitates to the oxygen-18 (18O) isotopic fractionations of breath CO2. In our observations, T1D exhibited considerable depletions of 18O-isotopes of CO2, whereas T2D manifested isotopic enrichments of 18O in breath CO2, thus unveiling a missing link of breath18O-isotopic fractionations in T1D and T2D. Our findings suggest that the alterations in erythrocytes CA activities may be the initial step of altered metabolism of T1D and T2D, and breath 18O-isotope regulated by the CA activity is a potential diagnostic biomarker that can selectively and precisely distinguish T1D from T2D and thus may open a potential unifying strategy for treating these diseases.

Insulin sensitivity index (ISI0, 120) potentially linked to carbon isotopes of breath CO2 for pre-diabetes and type 2 diabetes.

New strategies for an accurate and early detection of insulin resistance are important to delay or prevent the acute onset of type 2 diabetes (T2D). Currently, insulin sensitivity index (ISI0,120) is considered to be a viable invasive method of whole-body insulin resistance for use in clinical settings in comparison with other invasive sensitivity indexes like homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). To investigate how these sensitivity indexes link the (13)C/(12)C-carbon isotopes of exhaled breath CO2 to pre-diabetes (PD) and type 2 diabetes in response to glucose ingestion, we studied excretion dynamics of (13)C/(12)C-isotopic fractionations of breath CO2. Here, we show that (13)C/(12)C-isotope ratios of breath CO2 were well correlated with blood glucose, insulin, glycosylated-hemoglobin as well as with HOMA-IR and 1/QUICKI. Conversely, the strongest correlation was observed between 1/ISI0,120 and breath CO2 isotopes. Consequently, we determined several optimal diagnostic cut-off points of 1/ISI0,120 and (13)CO2/(12)CO2-isotope ratios to distinctively track the evolution of PD prior to the onset of T2D. Our findings suggest that isotopic breath CO2 is a novel method for accurate estimation of ISI0,120 and thus may open new perspectives into the isotope-specific non-invasive evaluation of insulin resistance for large-scale real-time diabetes screening purposes.

Oxygen-18 isotope of breath CO2 linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes.

Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( (18)O)-isotopic fractionations of CO2. To investigate how CA activity links the (18)O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of (18)O/ (16)O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D. Here we show that the post-dose CA activity in both T2D and PD was markedly enhanced, whereas the non-diabetic controls (NDC) exhibited a considerable reduction in post-dose CA activity when compared with their basal CA activities. However, T2D and PD exhibited isotopic enrichments of (18)O in breath CO2, while a marked depletion of (18)O in CO2 was manifested in NDC. Thus, the isotopic enrichments and depletions of (18)O in breath CO2 were well correlated with the changes in CA activities for controls, PD and T2D. Our findings suggest the changes in CA activities in erythrocytes may contribute to the pathogenesis of T2D and the breath C (18)O (16)O regulated by the CA activity as a potential biomarker for non-invasive assessment of T2D, and thus may open a new method for treating T2D.

Residual gas analyzer mass spectrometry for human breath analysis: a new tool for the non-invasive diagnosis of Helicobacter pylori infection.

A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection through ¹³C-urea breath analysis. The present RGA-based mass spectrometry (MS) method is capable of measuring high-precision ¹³CO2 isotope enrichments in exhaled breath samples from individuals harboring the H. pylori infection. The system exhibited 100% diagnostic sensitivity, and 93% specificity alongside positive and negative predictive values of 95% and 100%, respectively, compared with invasive endoscopy-based biopsy tests. A statistically sound diagnostic cut-off value for the presence of H. pylori was determined to be 3.0‰ using a receiver operating characteristic curve analysis. The diagnostic accuracy and validity of the results are also supported by optical off-axis integrated cavity output spectroscopy measurements. The δ¹³(DOB)C‰ values of both methods correlated well (R² = 0.9973 at 30 min). The RGA-based instrumental setup described here is simple, robust, easy-to-use and more portable and cost-effective compared to all other currently available detection methods, thus making it a new point-of-care medical diagnostic tool for the purpose of large-scale screening of the H. pylori infection in real time. The RGA-MS technique should have broad applicability for ¹³C-breath tests in a wide range of biomedical research and clinical diagnostics for many other diseases and metabolic disorders.

Non-invasive 13C-glucose breath test using residual gas analyzer-mass spectrometry: a novel tool for screening individuals with pre-diabetes and type 2 diabetes.

We report, for the first time, the clinical feasibility of a novel residual gas analyzer mass spectrometry (RGA-MS) method for accurate evaluation of the (13)C-glucose breath test ((13)C-GBT) in the diagnosis of pre-diabetes (PD) and type 2 diabetes mellitus (T2D). In T2D or PD, glucose uptake is impaired and results in blunted isotope enriched (13)CO2 production in exhaled breath samples. Using the Receiver operating characteristics (ROC) curve analysis, an optimal diagnostic cut-off point of the (13)CO2/(12)CO2 isotope ratios expressed as the delta-over-baseline (DOB) value, was determined to be δDOB(13)C‰ = 28.81‰ for screening individuals with non-diabetes controls (NDC) and pre-diabetes (PD), corresponding to a sensitivity of 100% and specificity of 94.4%. We also determined another optimal diagnostic cut-off point of δDOB(13)C‰ = 19.88‰ between individuals with PD and T2D, which exhibited 100% sensitivity and 95.5% specificity. Our RGA-MS methodology for the (13)C-GBT also manifested a typical diagnostic positive and negative predictive value of 96% and 100%, respectively. The diagnostic accuracy, precision and validity of the results were also confirmed by high-resolution optical cavity enhanced integrated cavity output spectroscopy (ICOS) measurements. The δDOB(13)C‰ values measured with RGA-MS method, correlated favourably (R(2) = 0.979) with those determined by the laser based ICOS method. Moreover, we observed that the effects of endogenous CO2 production related to basal metabolic rates in individuals were statistically insignificant (p = 0.37 and 0.73) on the diagnostic accuracy. Our findings suggest that the RGA-MS is a valid and sufficiently robust method for the (13)C-GBT which may serve as an alternative non-invasive point-of-care diagnostic tool for routine clinical practices as well as for large-scale diabetes screening purposes in real-time.