Why is premixed insulin the preferred insulin? Novel answers to a decade-old question.

A wide range of sources have been used to create an equally wide range of types of insulin (rapid acting, fast acting, premixed, intermediate acting and long acting). While some of these insulins are no longer in clinical use, others are being used extensively across the world. Premixed insulin is the most frequently prescribed and used insulin in Asia; basal insulin is more extensively used in USA. As compared with basal insulin alone, premixed regimens tend to lower HbA1c to a larger degree while providing enhanced convenience. It is a challenge for diabetologists to assess the conflicting guidelines and decide which one to follow. This is especially true with regard to choosing appropriate insulin for initiation of therapy. Besides, ethnicity may play a key role in determining choice of insulin therapy among different populations. Here, the authors discuss the various factors, pharmacological as well as psychological, that have made premixed insulins the preferred insulin for type 2 diabetes in India and the many parts of Asia. The authors utilize well known theories of psychology, namely generalization, cognitive dissonance and concordance to provide a rational explanation for the preference for premixed insulin that Indian people with diabetes, and their physicians, have.

Diagnosis of gestational diabetes mellitus in the community.

BACKGROUND AND OBJECTIVE: Diabetes in Pregnancy Study Group India (DIPSI) recommends 2-h Plasma glucose (PG) > or = 140 mg/dL with 75g oral glucose load to diagnose GDM, akin to WHO criteria. Recently, International Association of Diabetes in Pregnancy Study Group (IADPSG) recommends any one value of Fasting plasma glucose (FPG) > or = 92 mg/ dL, 1-h PG > or = 180 mg/dL or 2-h PG > or = 153 mg/dL to diagnose GDM. The objective of this study was to find out whether DIPSI guidelines could still be continued to diagnose GDM in our country, as this requires one blood test compared to three tests of IADPSG, which is expensive. METHOD: Consecutive pregnant women (N = 1463) underwent 75g oral glucose tolerance test (OGTT). The proportion of GDM was computed based on IADPSG and DIPSI criteria and the discordant pair of diagnosing GDM was examined by McNemar test. Analysis was two tailed and P-value <0.05 was considered for statistical significance. RESULT: The prevalence of GDM was 14.6% (N = 214) by IADPSG criteria and 13.4% (n = 196) by DIPSI criteria. The discordant pair between the two criteria examined by McNemar's test indicated that there was no statistical significance (P = 0.21) and thereby implying a close agreement between these two procedures. CONCLUSION: DIPSI procedure is cost-effective, without compromising the clinical equipoise and can be continued to diagnose GDM in our country, as well as other less resource countries.

Blockchain technology in supply chain management: an organizational theoretic overview and research agenda.

Blockchain technology is touted as a game-changer. Many experts consider blockchain technology as one of the disruptive innovations. Following significant success in the banking and finance sector, blockchain technology has found significant success in all fields, including health, manufacturing, transportation, disaster relief operations, and many others. Recently, the academician has contributed significantly towards understanding blockchain technology and its application in the management field. To understand how the literature on blockchain technology in the supply chain has progressed, we undertook an extensive review of the literature published in peer-reviewed journals using databases such as SCOPUS. We have further classified our literature into four stages (pre-adoption, adoption, implementation, and application). Finally, we synthesized the findings of the study and proposed a research framework to explain how an organization can build supply chain resilience and enhance supply chain performance with the help of blockchain technology. Finally, we have noted the limitations of the study and future research directions.

Insulin therapy at onset of type 2 diabetes mellitus--a new concept.

In this study, insulin therapy was initiated at onset of disease in patients whose fasting blood glucose was more than 250 mg/dl. All enrolled subjects were treated with human premixed insulin (30/70) administered subcutaneously twice daily before breakfast and before dinner. A total of 113 subjects entered the study fulfilling the inclusion criteria. Good glycaemic control was achieved in a few days. The dosage requirement of insulin came down gradually after control was achieved as manifest by hypoglycaemia--leading to withdrawal of insulin. Some of them were managed with diet and exercise alone. Others required small doses of oral antidiabetic agents (OAD). There were no cases of secondary failure to OADs. Ten cases are on average duration of follow-up of 10 years. Two cases are under good control with diet and exercise alone, seven on treatment with oral hypoglycemic agents and one of them requiring insulin to maintain HbAlc below 7%. Thus insulin therapy at onset provides an opportunity to correct all the underlying pathogenic mechanisms, i.e., glucotoxicity, lipotoxicity and prevents beta cell apoptosis and suppresses inflammation, leading to beta cell protection. Such timely intervention provides long term benefits, laying the foundation for the concept of beta cell preservation rather that only replacing beta cell function. Hence we propose that all patients with type 2 diabetes should be offered insulin therapy at the onset of their diabetes for a period of 2-4 weeks.

Analysis of canine myeloid-derived suppressor cells (MDSCs) utilizing fluorescence-activated cell sorting, RNA protection mediums to yield quality RNA for single-cell RNA sequencing.

Fluorescence-activated cell sorting (FACS) is a branch of flow cytometry that allows for the isolation of specific cell populations that can then be further analyzed by single-cell RNA sequencing (scRNA-seq). When utilizing FACS for population isolation prior to sequencing, it is essential to consider the protection of RNA from RNase activity, environmental conditions, and the sorting efficiency to ensure optimum sample quality. This study aimed to optimize a previously published MDSC flow cytometry strategy to FACS sort canine Myeloid-Derived Suppressor Cells (MDSC) with various permutations of RNAlater ™ and RiboLock™ before and after FACS sorting. Concentrations of RNAlater™ greater than 2 % applied before flow analysis affected cell survival and fluorescence, whereas concentrations ≤ 2 % and time ≤ 4 h had little to no effect on cells. To shorten the procedural time and to enhance the sorting of rare populations, we used a primary PE-conjugated CD11b antibody and magnetic column. The combination of RiboLock™ pre- and post-sorting for FACS provided the best quality RNA as determined by the RNA integrity number (RIN ≥ 7) for scRNA-seq in a normal and dog and a dog with untreated oral melanoma dog. As proof of principle, we sequenced two samples, one from a normal dog another from a dog with untreated oral melanoma. Applying scRNA-Seq analysis using the 10X Genomic platform, we identified 6 clusters in the Seurat paired analysis of MDSC sorted samples. Two clusters, with the majority of the cells coming from the melanoma sample, had genes that were upregulated (> log2); these included MMP9, MMP1, HPGD, CPA3, and GATA3 and CYBB, CSTB, COX2, ATP6, and COX 17 for cluster 5 and 6 respectively. All genes have known associations with MDSCs. Further characterization using pathway analysis tools was not attempted due to the lower number of cells sequenced in the normal sample. The benefit deriving from the results of the study helped to gain data consistency when working with cells prone to RNase activity, and the scRNA-seq provided data showing transcriptional heterogeneity in MDSC populations and potentially identifying previously unreported or rare cell populations.

Sequence analysis of morbillivirus CD150 receptor-Signaling Lymphocyte Activation Molecule (SLAM) of different animal species.

Signaling Lymphocyte Activation Molecule-SLAM (CD150) molecule has been reported as a putative receptor for most morbilliviruses for their respective host species. In this study, we determined the complete nucleotide sequence of the gene coding for the morbillivirus receptor-SLAM from the four species, namely, goat (Capra hircus), sheep (Ovis aries), Indian cattle (Bos indicus), and buffalo (Bubalus bubalis). The nucleotide (nt) open reading frame sequence of SLAM gene in all the four species studied was 1017 nucleotides in length encoding a polypeptide of 339 amino acids (aa), similar to Bos taurus, but different from canine, human, marmoset, and mouse SLAM, which were 1029, 1008, 1011, and 1032 nts, respectively, in length, and coding for 343, 336, 337, and 344 aa, respectively. Sequence analysis revealed 96.3-98.5% and 92.9-96.8% identities among the four species at the nt and aa level, respectively. Sequence diversity at aa level between various species revealed that the critical functional region of SLAM protein among different species is relatively conserved, thereby facilitating this molecule to act as a receptor for morbillivirus. Phylogenetic relationship based on the aa sequences of SLAM protein revealed that caprine, ovine, cattle, and buffalo fall under a defined cluster but caprine SLAM is more closely related to ovine, followed by bovine.

Vehicle routing for a mid-day meal delivery distribution system.

This paper considers the distribution system of a school feeding program (mid-day meals), wherein a set of delivery vehicles transfer cooked food from a kitchen facility to various schools within a specified delivery deadline. The food is required to be delivered before the lunch period, which is consistent across all the schools. A delay in food delivery can deprive students of their lunch, and, therefore, designing the vehicle routes for such distribution systems and maintaining a strict delivery deadline becomes critical. The resultant problem is identified as a vehicle routing problem with a common due date (VRPCDD). We provide a formulation for the VRPCDD and thereby focus on suggesting solution methods. In addition, we also demonstrate the practical application of VRPCDD by focusing on a real-life problem of a mid-day meal provider operating in the Chhattisgarh province of India.

Characterization of myeloid-derived suppressor cells and cytokines GM-CSF, IL-10 and MCP-1 in dogs with malignant melanoma receiving a GD3-based immunotherapy.

Melanoma in humans and canines is an aggressive and highly metastatic cancer. The mucosal forms in both species share genetic and histopathologic features, making dogs a valuable spontaneous disease animal model. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells of myeloid origin with immunosuppressive capabilities, which are increased in many human cancers and contribute to tumor immune evasion. They are a possible target to improve immunotherapy outcomes. Current information regarding MDSCs in canines is minimal, limiting their use as translational model for the study of MDSCs. The objective of this study was to characterize major MDSCs subsets (monocytic and polymorphonuclear) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in canines with malignant melanoma and to evaluate changes in MDSCs and the cytokines over time in response to a GD3-based active immunotherapy. Whole blood and serum collected from 30 healthy controls and 33 patients enrolled in the University of Florida melanoma vaccine trial were analyzed by flow cytometry with canine specific CD11b, MHCII and anti-human CD14 antibodies to assess ostensibly polymorphonuclear-MDSC (CD11b+ MHCII- CD14-) and monocytic-MDSC (CD11b+ MHCII- CD14+) subsets. IL-10, MCP-1 and both MDSCs subsets were significantly elevated in melanoma dogs versus controls. Both MDSCs subsets decreased significantly following GD3-based immunotherapy administration but no significant changes in cytokines were seen over time. To our knowledge, this is the first report documenting increased monocytic-MDSCs in canine melanoma. This is consistent with human malignant melanoma data, supporting dogs as a valuable model for therapeutic intervention studies.

Role of yoga in diabetes.

The science of yoga is an ancient one. It is a rich heritage of our culture. Several older books make a mention of the usefulness of yoga in the treatment of certain diseases and preservation of health in normal individuals. The effect of yogic practices on the management of diabetes has not been investigated well. We carried out well designed studies in normal individuals and those with diabetes to assess the role of yogic practices on glycaemic control, insulin kinetics, body composition exercise tolerance and various co-morbidities like hypertension and dyslipidemia. These studies were both short term and long-term. These studies have confirmed the useful role of yoga in the control of diabetes mellitus. Fasting and postprandial blood glucose levels came down significantly. Good glycaemic status can be maintained for long periods of time. There was a lowering of drug requirement and the incidence of acute complications like infection and ketosis was significantly reduced. There were significant changes in the insulin kinetics and those of counter-regulatory hormones like cortisol. There was a decrease in free fatty acids. There was an increase in lean body mass and decrease in body fat percentage. The number of insulin receptors was also increased. There was an improvement in insulin sensitivity and decline in insulin resistance. All these suggest that yogic practices have a role even in the prevention of diabetes. There is a beneficial effect on the co-morbid conditions like hypertension and dyslipidemia.

Development of an indirect ELISA for the detection of antibodies against Peste-des-petits-ruminants virus in small ruminants.

Peste des petits ruminants (PPR) is an acute, febrile, highly contagious and economically important viral disease of small ruminants. A polyclonal antibody based indirect ELISA was developed for detection of antibodies to PPR virus in the serum samples of goats and sheep using purified PPR viral antigen propagated in Vero cell culture. A threshold (cut-off) value was set as twice the mean of the negative population based on the distribution of known negative serum samples in respect of PPR virus antibodies in the test. A total of 1544 serum samples from goats and sheep were screened by indirect ELISA and competitive ELISA. The indirect ELISA compared very well with competitive ELISA, with a high degree of specificity (95.09%) and sensitivity (90.81%). When compared with virus neutralization test, the present assay had 100% specificity and 80% sensitivity. With serum samples, the assay could clearly differentiate animals from the infected population from uninfected ones. These results suggest that the indirect ELISA may be a good alternative tool to competitive ELISA for seroepidemiological surveys.

Risk factors for coronary heart disease in type II diabetes mellitus.

Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. An attempt has been made to evaluate the risk factors for coronary heart disease in type II diabetics. In the present study the levels of fasting and postprandial plasma glucose, total cholesterol, low density lipoproteins, triglycerides were high and the levels of high density lipoproteins were low in the type II diabetics compared to controls. The markers of free radical induced injury i.e. malondialdehyde and nitrite/nitrate were high while total antioxidant status a marker for antioxidant protection against reactive oxygen species was low in diabetics compared to controls. The study therefore suggests the importance of assessing these markers of oxidative stress and antioxidant capacity along with the other routine investigations in diabetic patients for initiating antioxidant therapy in addition to primary and secondary preventive measures to mitigate the devastating consequences of diabetes leading to coronary heart disease.

Specific immune responses in typhoid fever & after TAB vaccination.

The specific immune responses to Salmonella typhi were investigated in 131 patients suffering from typhoid fever and 34 healthy individuals after TAB vaccination. A proportion of individuals failed to develop either specific humoral or cell mediated immune responses. About 5 per cent of the patients with natural infection and nearly 9 per cent of the vaccine recipients failed to develop both the responses. Frequent reinfection and carrier state, and lack of absolute protection following TAB vaccination could be due to the inability of a proportion of naturally infected and TAB vaccinated individuals to mount sufficient specific immune responses, due to the same mechanism.

Comparison of effects of yoga & physical exercise in athletes.

The effect of pranayama a controlled breathing practice, on exercise tests was studied in athletes in two phases; sub-maximal and maximal exercise tests. At the end of phase I (one year) both the groups (control and experimental) achieved significantly higher work rate and reduction in oxygen consumption per unit work. There was a significant reduction in blood lactate and an increase in P/L ratio in the experimental group, at rest. At the end of phase II (two years), the oxygen consumption per unit work was found to be significantly reduced and the work rate significantly increased in the experimental group. Blood lactate decreased significantly at rest in the experimental group only. Pyruvate and pyruvate-lactate ratio increased significantly in both the groups after exercise and at rest in the experimental group. The results in both phases showed that the subjects who practised pranayama could achieve higher work rates with reduced oxygen consumption per unit work and without increase in blood lactate levels. The blood lactate levels were significantly low at rest.

Neurological emergencies--diabetes management.

Diabetes can affect the nervous system in several ways. Of all the neurological complications of diabetes, peripheral neuropathy is by far the commonest and has been extensively studied. The involvement of central nervous system can be in several forms. The underlying damage may be due to involvement of the large and small cerebral blood vessels as also due to metabolic derangement caused by prolonged hypoglycemia, anoxia or ketoacidosis. The neurological emergencies that occur in diabetes can be: 1) atherothrombotic and lacunar strokes; 2) convulsive disorder in the setting of both hypo and hyperglycemia; 3) coma; 4) cranial neuropathies; and 5) acute proximal muscle weakness. In patients with diabetes, atherothrombotic stroke is associated with poor outcome. Hyperglycemia at the time of stroke is an important risk factor for an adverse outcome than chronic stable diabetic state. Proper management of diabetes in these acute situations is crucial for a better outcome of the underlying disease process.

DiabCare Asia--India Study: diabetes care in India--current status.

AIM: To investigate the relationship between diabetes control, management and late complications in a subset of urban Indian diabetes population treated at tertiary diabetes care centres and measure the quality of management to set benchmarks for future improvement. METHODOLOGY: The study population consisted of 100 consecutive review patients treated for more than one year at each of the 26 participating centres. HbA1c was estimated centrally by Bio-Rad Variant method. The methods used to diagnose diabetic complications varied among centres, depending on the doctor's standard clinical examination. A more detailed methodology was eschewed for reason of brevity of the data collection form, and lack of standardisation of methods. Similarly, the assessment of renal function was performed via a variety of methods, namely dipstick proteinuria, a 24 hour urinary excretion assay, presence of microalbuminuria and serum creatiine concentration; retinopathy was detected using fundoscopy. Data was collected in a standardized data collection form, entered into an SAS database, validated and descriptive analysis performed. RESULTS: A total of 2,269 subjects with valid relevant data formed the study population. Subjects had a mean age of 53.3 +/- 13 years. The mean age at onset of diabetes was 43.6 +/- 12.2 years, with a mean diabetes duration of 10.0 +/- 6.9 years. Type 2 diabetics constituted 90.6% of the patients. Approximately half the patients had poor control (HbA1c > 2% points above upper limit of normal and FBG > 139 mg/dl). Mean HbA1c (central laboratory) was 8.9 +/- 2.1% and FBG 150 +/- 59 mg/dl. Over 54% patients had severe late complications, apart from a high frequency of associated hyperlipidemia. Mean HbA1c level and frequency of complications was higher in patients with longer diabetes duration. Frequency of self-monitoring was low. Only 4% of patients were on diet therapy, 53.9% were receiving oral hypoglycemic agents (OHAs), 22% were receiving insulin and 19.8% a combination of insulin and OHAs. Frequency of insulin usage was higher amongst patients with longer diabetes duration. CONCLUSIONS: This large multi-centre collaborative observational study shows that type 2 diabetes begins at an early age amongst Indians. With increasing duration of diabetes, glycemic control deteriorates leading to late complications. Diabetes care in India leaves much to be desired. Concerted efforts to increase awareness amongst health professionals to improve diabetes care are urgently needed. The study by increasing awareness about the current status of diabetes care provides a useful benchmark to plan future improvements.

Baseline characteristics of the IMPROVE control study population: A study to evaluate the effectiveness of a standardized healthcare professionals training program.

INTRODUCTION: The IMPROVE Control Training program was designed by Indian Academy of Diabetes (IAD), and a non-intervention study was conducted to evaluate the effectiveness of this standardized healthcare professionals (HCPs) training program on achieving treatment goals in patients with diabetes mellitus and its impact on standard of care. MATERIALS AND METHODS: This multi-center, parallel group, open-label, non-randomized, non-intervention study included patients with type 2 diabetes who had an HbA1c >9 at time of diagnosis or an HbA1c >7% even after 6 months of initiation of therapy with anti-diabetic agents (Oral anti diabetic agents (OADs) and/or insulin). The data recorded at baseline included demographic characteristics, medical history, and the treatment regimens. RESULTS: The study included 20,493 patients with diabetes, of which 13,295 (64.9%) were men. The mean [standard deviation (SD)] duration of diabetes was 6.4 (4.2) years and 6608 (32.2%) reported complications of diabetes. Poor glycemic control [HbA1c = 9.4 (1.3), FPG (mg/dl) = 181.2 (45.7); mean (SD)] was observed. The postprandial glucose was also high [post-breakfast, lunch, and dinner values in mg/dl were 263.6 (68.5), 278.1 (69.6), and 250.2 (63.7), respectively] in these patients. Failure of OADs was the most common reason cited for initiation of insulin. Premixed insulin was rated the regimen of choice for initiating therapy by the physicians (62.2% vs. 34.5% who preferred basal insulin). CONCLUSION: The baseline results confirm the poor glycemic control and the delayed initiation and/or inadequacy of treatment in subjects with type 2 diabetes. These results also highlight the need for early and optimal insulin-based therapy.

Physicians' perceptions of a national consensus guideline on insulin therapy: Data from the IMPACT study.

INTRODUCTION: The effectiveness and impact of the Indian insulin guideline in clinical practice was evaluated by the Improving Management Practices and Clinical Outcomes in Type 2 Diabetes (IMPACT) Study. The study also evaluated the participating physicians' perceptions on the use of IIG versus RCP for management of diabetes. MATERIALS AND METHOD: This 26 week multicenter, open label, randomized, prospective study aimed to evaluate effectiveness of Indian insulin guideline (IIG) versus routine clinical practice (RCP) in patients with type 2 diabetes (T2D). RESULTS: Out of 426 physicians who completed the physicians' perception questionnaire, 189 (44.4%) felt that it was "easy" to initiate insulin in their patients using IIG. Cost of therapy (52.3%), followed by poor adherence (40.3%), and lack of motivation among physicians (40.4%) were the most important reasons cited for delay in initiation of insulin therapy. Two hundred and thirty three (54.7%) physicians felt that insulin titration was made "easy" in their patients using IIG, while 104 (24.4%) had a neutral approach. A total of 222 physicians (52.1%) felt it was "convenient" applying IIG in their practice, and 239 (67.8%) physicians felt "satisfied" with using IIG for achieving the targeted HbA1c <7%. One hundred and seventy seven (41.5%) physicians felt that there was scope for improving the IIG further by simplifying and revising the titration charts [117 (27.5%)]. CONCLUSION: Primary care physicians in India have perceived the IIG to be easy algorithm to initiate and titrate insulin therapy. These results will encourage the use and facilitate future revision of the guideline.

Improving management practices and clinical outcomes in type 2 diabetes study: Prevalence of complications in people with type 2 diabetes in India.

INTRODUCTION: Diabetes is the fourth leading cause of disease-related death and almost 80% of diabetes-related deaths occur in developing countries. Optimal glycemic control, in particular HbA1c level less than 7% with effective management of dyslipidemia and hypertension can reduce development of diabetes-related complications. Delay in initiating/or optimizing appropriate anti-diabetic therapy including insulin could be a possible cause of the increase in complications. METHOD: Improving management practices and clinical outcomes in type 2 diabetes (IMPACT) was a prospective, open-label, 26-week, comparative, multi-center study to compare efficacy and safety of the Indian insulin guideline (IIG) group versus routine clinical practice (RCP) group in type 2 diabetes patients. A total of 20,653 subjects from 885 centers across India were enrolled. RESULTS: A total of 4695 patients (22.7%) (IIG, 4113 [22.6%]; RCP, 582 [23.5%]) had macrovascular complications and 8640 patients (41.8%) (IIG, 7486 [41.2%]; RCP, 1154 [46.6%]) had microvascular complications. Of 4695 patients with macrovascular complications, 2850 patients (60.7%) had coronary heart disease followed by 1457 patients (31.0%) with peripheral vascular disease. Of all the microvascular complications recorded, 5627 patients (65.1%) had peripheral neuropathy followed by 3313 patients (38.3%) with retinopathy. CONCLUSION: The rates of complications were high in patients with type 2 diabetes at the time of being initiated on insulin therapy in India.