Evolution of Guideline Recommendations on Insulin Therapy in Type 2 Diabetes Mellitus Over the Last Two Decades: A Narrative Review.

The prevalence of type 2 diabetes mellitus has been increasing worldwide. As the therapeutic options for type 2 diabetes mellitus have evolved over the last 2 decades, national and global guidelines related to type 2 diabetes mellitus pharmacotherapy issued by various organizations have tended to vary in their recommendations. This narrative review aimed to analyze the key recommendations by major global and national guidelines on the initiation of insulin therapy in patients with type 2 diabetes mellitus over the last 20 years. Strategies for insulin therapy for titration and intensification were also assessed. All guidelines recommend initiation of insulin (basal/ premixed/other formulations) when glycemic targets are not achieved despite lifestyle measures and oral antidiabetic drugs. In the recent decade, early initiation of insulin has been recommended when the glycated hemoglobin levels are >10% or blood glucose levels are ≥300 mg/dL (16.7 mmol/L). Initiation is recommended at a dose of 10 units or 0.1-0.2 U/kg. Titration is advised to achieve the optimal dosage, while intensification is recommended when glycemic targets are not achieved despite titrating to an acceptable level. Glucose monitoring at periodic intervals is recommended for adequate glycemic control. The guidelines further suggest that the choice of insulin should be individualized, considering the clinical status of patients with type 2 diabetes mellitus. The physicians as well as patients should be a part of the decisions made regarding the therapeutic choice of regimen, preparation, and delivery device.

Estimating the total incidence of type 1 diabetes in children and adolescents aged 0-19 years from 1990 to 2050: a global simulation-based analysis.

BACKGROUND: Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country. METHODS: We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration. FINDINGS: We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050. INTERPRETATION: Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa. FUNDING: Novo Nordisk.

Achievement of guideline recommended diabetes treatment targets and health habits in people with self-reported diabetes in India (ICMR-INDIAB-13): a national cross-sectional study.

BACKGROUND: There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among adults with self-reported diabetes. METHODS: The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbA1c of less than 7·0% (A), blood pressure control was defined as less than 140/90 mm Hg (B), and the LDL cholesterol target was defined as less than 100 mg/dL (C). ABC control was defined as the proportion of individuals meeting glycaemic, blood pressure, and LDL cholesterol targets together. We also performed multiple logistic regression to assess the factors influencing achievement of diabetes treatment targets. FINDINGS: Between Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (<10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose. INTERPRETATION: Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare.

Randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of transient receptor potential ankyrin 1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function.

ABSTRACT: Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.

Insulinization in T2DM with Basal Analogues During COVID-19 Pandemic: Expert Opinion from an Indian Panel.

The ongoing global pandemic of the coronavirus disease 2019 (COVID-19) has placed a severe strain on the management of chronic conditions like diabetes. Optimal glycemic control is always important, but more so in the existing environment of COVID-19. In this context, timely insulinization to achieve optimal glycemic control assumes major significance. However, given the challenges associated with the pandemic like restrictions of movement and access to healthcare resources, a simple and easy way to initiate and optimize insulin therapy in people with uncontrolled diabetes is required. With this premise, a group of clinical experts comprising diabetologists and endocrinologists from India discussed the challenges and potential solutions for insulin initiation, titration, and optimization in type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic and how basal insulin can be a good option in this situation owing to its unique set of advantages like lower risk of hypoglycemia, ease of training, need for less monitoring, better adherence, flexibility of using oral antidiabetic drugs, and improved quality of life compared to other insulin regimens. The panel agreed that the existing challenges should not be a reason to delay insulin initiation in people with uncontrolled T2DM and provided recommendations, which included potential solutions for initiating insulin in the absence or restriction of in-person consultations; the dose of insulin at initiation; the type of insulin preferred for simplified regimen and best practices for optimal titration to achieve glycemic targets during the pandemic. Practical and easily implementable tips for patients and involvement of stakeholders (caregivers and healthcare providers) to facilitate insulin acceptance were also outlined by the expert panel. Simplified and convenient insulin regimens like basal insulin analogues are advised during and following the pandemic in order to achieve glycemic control in people with uncontrolled T2DM.

Suboptimal glycemic control among subjects with diabetes mellitus in India: a subset analysis of cross-sectional wave-7 (2016) data from the International Diabetes Management Practices Study (IDMPS).

OBJECTIVE: To assess the real-world management practices of subjects with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) in India. METHODS: This cross-sectional study was conducted between 7 March 2016 and 15 May 2016 in India as part of the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). Adult subjects with T1DM or T2DM visiting physicians during a 2-week recruitment period were included. RESULTS: A total of 55 physicians included 539 subjects who met eligibility criteria. Of 495 subjects with T2DM, 303 were treated with oral glucose lowering drugs (OGLDs) only, 158 were treated with OGLD + insulin, and 27 received insulin only. Among 44 subjects with T1DM receiving insulin, 13 (29.5%) were also treated with OGLD therapy. The most commonly used insulin regimens were basal alone (69/184; 37.5%) and premixed alone (63/184; 34.2%) in subjects with T2DM, and basal + prandial insulin (24/44; 54.5%) in subjects with T1DM. Proportions of subjects achieving glycemic targets were low [glycated haemoglobin (HbA1c) <7%: T1DM = 7.3% (3/44), T2DM = 25.2% (106/495); as targeted by the treating physician: T1DM = 31.8% (14/44), T2DM = 32.1% (59/185); global target: T1DM = 4.8% (2/42) and T2DM = 1.7% (8/482)]. In subjects with T2DM, HbA1c <7% was noted in 11/22 subjects receiving insulin only and 76/260 receiving only OGLDs. Lack of experience in self-managing insulin dosing, poor diabetes education and failure to titrate insulin dosages were the main reasons for non-achievement of glycemic targets. CONCLUSION: Timely insulinization, education and empowerment of people with diabetes may help improve glycemic control in India.

Best Practices and Tools for Titrating Basal Insulins: Expert Opinion from an Indian Panel via the Modified Delphi Consensus Method.

AIM: To develop an evidence-based expert group consensus document on the best practices and simple tools for titrating basal insulins in persons with type 2 diabetes mellitus (T2DM). BACKGROUND: Glycemic control is suboptimal in a large proportion of persons with T2DM, despite insulin therapy, thereby increasing the risk of potentially severe complications. Early initiation of insulin therapy and appropriate dose titration are crucial to achieving glycemic targets. Attitudes and practices among healthcare professionals (HCPs) and perceptions about insulin therapy among persons with diabetes contribute largely to suboptimal glycemic control. Improving HCP-patient communication, encouraging the use of additional educational tools, and providing support for the titration process to increase confidence, both at the initiation visit and at home, facilitate the optimization of dose titration. In Indian settings, specific guidelines and a consensus statement are lacking on the optimal insulin initiation dose, frequency of dose titration, and basal insulin profile needed to achieve optimal titration. In clinical practice, physicians and persons with diabetes often do not adhere to the titration algorithms that currently exist for the purpose of achieving optimal titration as they perceive these to be very cumbersome. In this context, a group of experts met at an advisory board meeting and arrived at a consensus on best practices for the titration of basal insulin in persons withT2DM in India, using the modified Delphi methodology. REVIEW RESULTS: After a review of evidence and further discussions, the expert group provided recommendations on insulin initiation dose, ideal period for titration in practice, titration regimen for use in practice, basal insulin profile for titration, and choosing a self-monitoring blood glucose schedule for titration. CONCLUSIONS: In the management of T2DM, insulin can be effectively titrated by following a few simple recommendations. The use of second-generation basal insulin aids in mitigating the risk of hypoglycemic events. The implementation of a simplified titration regimen is crucial to achieving glycemic targets and long-term treatment goals.

Liraglutide as add-on to sodium-glucose co-transporter-2 inhibitors in patients with inadequately controlled type 2 diabetes: LIRA-ADD2SGLT2i, a 26-week, randomized, double-blind, placebo-controlled trial.

AIM: To compare the effect of liraglutide or placebo added on to sodium-glucose co-transporter-2 inhibitor (SGLT2i) ± metformin on glycaemic control in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with type 2 diabetes on a stable SGLT2i dose ± metformin (with HbA1c 7.0%-9.5% and body mass index [BMI] ≥ 20 kg/m2 ) were randomized 2:1 to add-on liraglutide 1.8 mg/day or placebo in this parallel, double-blind, multinational trial. Primary and confirmatory secondary endpoints were changes in HbA1c and body weight from baseline to week 26, respectively. The proportions of patients achieving HbA1c (<7.0%) targets and safety events after week 26 were also assessed. RESULTS: Of 303 patients randomized (one in error), 280 completed treatment. Mean changes in HbA1c from baseline to week 26 with liraglutide (n = 202) and placebo (n = 100) were - 0.98% and - 0.30%, respectively (estimated treatment difference [ETD]: -0.68% [95% CI: -0.89, -0.48]; P < 0.001). Mean body weight changes from baseline were - 2.81 versus -1.99 kg, respectively (ETD: -0.82 kg [95% CI: -1.73, 0.09]; P = 0.077); 51.8% of liraglutide-treated patients achieved HbA1c < 7.0% versus 23.2% receiving placebo (odds ratio: 5.1 [95% CI: 2.67, 9.87]; P < 0.001). More patients treated with liraglutide reported ≥1 treatment-emergent adverse events (66.3%) versus placebo (47.0%). CONCLUSIONS: Liraglutide significantly improved glycaemic control compared with placebo in patients with type 2 diabetes, insufficiently controlled with SGLT2is with/without metformin, with no unexpected safety findings.

Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program.

INTRODUCTION: The efficacy and safety of insulin degludec/liraglutide (IDegLira) has been evaluated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase 3 clinical trial program. In this post hoc analysis, we compared the efficacy and safety of IDegLira in the Indian subpopulation with the results from the global trial population of DUAL trials. The analysis includes participants uncontrolled on oral antidiabetic drugs (OADs) in DUAL I and DUAL IV and participants uncontrolled on basal insulin and OADs in DUAL II. METHODS: Three phase 3 trials were included in the analysis: DUAL I extension (IDegLira vs. insulin degludec or liraglutide 1.8 mg in participants uncontrolled on metformin ± pioglitazone; 52 weeks; n = 1663), DUAL IV (IDegLira vs. placebo as an add-on to a regimen of sulfonylurea ± metformin; 26 weeks; n = 435) and DUAL II (IDegLira vs. insulin degludec in participants uncontrolled on basal insulin + OADs; 26 weeks; n = 398). There were 251, 64 and 64 participants, respectively, at the Indian sites. RESULTS: In the Indian subpopulations, the reductions in glycated hemoglobin (HbA1c) with IDegLira were substantial [DUAL I: 1.96% (-21 mmol/mol); DUAL IV: -1.40% (-15 mmol/mol); DUAL II: -2.20% (-24 mmol/mol)] and significantly greater than those in the comparators in each trial. IDegLira was generally weight-neutral after the administration of OADs (-0.3 and +0.6 kg in DUAL I and DUAL IV) and resulted in weight loss after the administration of basal insulin (-2.1 kg in DUAL II). Hypoglycemia rates were 1.98, 1.08 and 0.37 events/patient-years of exposure (PYE) for IDegLira, insulin degludec and liraglutide in DUAL I, 4.06 and 0.36 events/PYE for IDegLira and placebo in DUAL IV and 1.16 and 0.83 events/PYE with IDegLira and insulin degludec in DUAL II. CONCLUSIONS: Results from the Indian subpopulations reflect those of the global study populations, supporting IDegLira as an effective and safe treatment option for people with type 2 diabetes inadequately controlled on OADs or basal insulin + OADs in the South Asian population. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01336023 (DUAL I), NCT01392573 (DUAL II), NCT01618162 (DUAL IV). FUNDING: Novo Nordisk A/S, Bagsvaerd, Denmark.

Diabetes insipidus: The other diabetes.

Diabetes insipidus (DI) is a hereditary or acquired condition which disrupts normal life of persons with the condition; disruption is due to increased thirst and passing of large volumes of urine, even at night. A systematic search of literature for DI was carried out using the PubMed database for the purpose of this review. Central DI due to impaired secretion of arginine vasopressin (AVP) could result from traumatic brain injury, surgery, or tumors whereas nephrogenic DI due to failure of the kidney to respond to AVP is usually inherited. The earliest treatment was posterior pituitary extracts containing vasopressin and oxytocin. The synthetic analog of vasopressin, desmopressin has several benefits over vasopressin. Desmopressin was initially available as intranasal preparation, but now the oral tablet and melt formulations have gained significance, with benefits such as ease of administration and stability at room temperature. Other molecules used for treatment include chlorpropamide, carbamazepine, thiazide diuretics, indapamide, clofibrate, indomethacin, and amiloride. However, desmopressin remains the most widely used drug for the treatment of DI. This review covers the physiology of water balance, causes of DI and various treatment modalities available, with a special focus on desmopressin.

Intensifying Insulin Therapy in Type 2 Diabetes: Choices & Challenges.

Insulin therapy remains the cornerstone of effective diabetes management. Timely intensification of insulin therapy reduces the progression of diabetes and the development of diabetes-related complications. Given that overall hyperglycaemia is a relative contribution of both fasting and postprandial hyperglycaemia, use of basal insulin alone may not achieve optimal glucose control due to its inability to cover postprandial glucose excursions. Intensifying therapy with addition of bolus insulin or switching to premixed insulin is a viable option in patients failing on basal alone therapy. Although the benefits of early insulin treatment are well established, a considerable delay in intensifying insulin therapy in patients with sub-optimal glycaemic control is still observed. Most of the patients and physicians are reluctant to intensify therapy due to the fear of hypoglycaemia, regimen complexity, and increased burden of multiple daily injections. In this context, there is a need for a flexible, alternative intensification option taking into account individual patient considerations to achieve or maintain individual glycaemic targets. An ideal insulin regimen should mimic physiological insulin release while providing optimal glycaemic control with low risk of hypoglycaemia, weight gain and fewer daily injections. The current paper reviews the challenges of insulin intensification in patients with type 2 diabetes mellitus poorly controlled on current treatment regimens.

Treatment essentials and training for health care providers.

The lack of awareness among health care providers (HCPs) is one of the biggest challenges for the management of patients with type 1 diabetes mellitus (T1DM) in India. Major challenges faced by HCPs include lack of awareness about the disease among general physicians and inadequately trained staff to deal with children with T1DM. The changing diabetes in children (CDiC) program is helping in overcoming these barriers faced by HCPs. CDiC provides treatment, monitoring tools, and education to children affected with T1DM and has been instrumental is developing various education and awareness tools.

Type 1 diabetes: Awareness, management and challenges: Current scenario in India.

Type 1 diabetes mellitus (T1DM) has a wide presence in children and has a high mortality rates. The disease, if left unmanaged, poses various challenges to the patient and healthcare providers, including development of diabetic complications and thus decreasing the life expectancy of the affected child. The challenges of T1DM include awareness of the disease that is very poor among the general public and also in parents of T1DM children along with the health care professionals. The challenge of lack of awareness of T1DM can be met by increasing public awareness programs, conducting workshops for diabetes educators regarding T1DM in children, newsletters, CMEs, online courses, and by structured teaching modules for diabetes educators. Diagnosis of T1DM was a challenge a few decades ago but the situation has improved today with diagnostic tests and facilities, made available even in villages. Investigation facilities and infrastructure, however, are very poor at the primary care level, especially in rural areas. Insulin availability, acceptability, and affordability are also major problems, compounded by the various types of insulin that are available in the market with a varied price range. But effective use of insulin remains a matter of utmost importance.

Efficacy without barriers to insulin therapy: lessons from the BEGIN trial programme.

Insulin degludec has been extensively studied in the BEGIN programme in a range of patients with type 1 or type 2 diabetes. The programme includes insulin-naive type 2 diabetes, insulin-treated type 2 and type 1 diabetes which are investigated as basal-bolus therapy, basal plus oral therapy, and basal vs. oral therapy and also the flexible dosing options. In all insulin degludec phase 3 trials, the efficacy of once daily insulin degludec was established, as insulin degludec being non-inferior to comparators in reducing HbA(1c). Also the flexible dosing option is an attractive feature of this insulin that mightimprove adherence to therapy and conceivably improve outcomes.

Consensus evidence-based guidelines for use of insulin pump therapy in the management of diabetes as per Indian clinical practice.

The use of insulin pump in diabetes is likely to increase with recent advances in technology. Although the evidence for the superiority of pumps over multiple daily injections (MDI) is inconsistent, data from accumulating uncontrolled studies indicate greater reductions in glycated haemoglobin in patients switching to continuous subcutaneous insulin infusion (CSII) from MDI therapy. Due to the variability in insulin requirements and sensitivity to CSII pumps, hyperglycaemia in these patients is managed by endocrinologists using individualised therapy. A panel of experts reviewed the existing guidelines and framed recommendations specific to the clinical practice in Indian conditions for use of CSII pumps in the management of hyperglycaemia. Selection of right patient with basic education, motivation and learning skills are essential for successful implementation of CSII therapy with sophisticated programmes. Rapid acting insulin analogues with better pharmacokinetic and pharmacodynamic profile, physical and chemical stability and compatibility with most commercially available insulin pumps are preferred over regular insulin to achieve safe and stable glycaemic control. Further, educating pump users on proper use of CSII pumps, insulin dose adjustments, and handling of accessories are recommended in the current consensus guidelines. Practice of self-monitoring of blood glucose and glycated haemoglobin levels are essential to adjust insulin dosage for the management of diabetes. Use of CSII pumps in special patient populations should be carefully assessed and initiated by endocrinologist. The proposed guidelines can form a basis for use of CSII pumps in the management of hyperglycaemia in the Indian scenario.

Adrenal incidentaloma: A puzzle for clinician.

An adrenal incidentaloma (AI) is a puzzle for clinician. In the era of widespread use of CT and MRI, it is becoming an increasingly frequent diagnosis. A detailed list of investigations is ordered to diagnose pathology responsible for AI. Most likely etiology of AI is pathology of AI is benign non-functional adenoma. But looking to the need of specific preoperative preparation for functional adrenal adenoma and importance of early diagnosis in adrenal carcinoma, a complete workup is essential. CT scan of adrenals with contrast gives maximum information about nature of lesion. In general, a lesion more than 6cm or a functioning AI or tumor signal intensity of more than 10HU on unenhanced image, significant enhancement on contrast and deenhancement in signal intensity of less than 50% is suggestive of carcinoma and must be removed. Those AI which are left for observation, also needs regular testing and if found functional on subsequent follow-up or if their size enlarge, they must be removed.

Evaluation of skin and subcutaneous tissue thickness at insulin injection sites in Indian, insulin naïve, type-2 diabetic adult population.

CONTEXT: Skin thickness of type-2 diabetic insulin naïve adult patients. BACKGROUND: We have limited data on skin and subcutaneous tissue thickness of Indian type-2 diabetic population. Objective of this study was to assess skin and subcutaneous tissue thickness in insulin naïve type-2 diabetic patients as this information may be useful for insulin injection technique. AIMS: To assess the skin and subcutaneous tissue thickness at insulin injection sites in insulin naïve, type-2 diabetic adult population across different body mass index (BMI). SETTINGS AND DESIGN: Observational study carried out at our institute. MATERIALS AND METHODS: One hundred and one insulin naïve type-2 diabetic subjects underwent skin thickness measurement using ultrasound at insulin administration sites. Skin and subcutaneous tissue thickness were measured and prints taken. Though, the sample size to be taken for the study was not calculated, the results obtained clearly show that the power of the study was 80%. RESULTS: At arm and thigh, the mean skin thickness was more in males as compared to females in the BMI range <23 kg/m(2) (P < 0.05). At abdomen, skin thickness was more in males in the BMI range 19-23 kg/m(2) (P < 0.05). Across all the BMIs, mean skin plus subcutaneous thickness at arm was more in females (P < 0.05) except for BMI >25 kg/m(2) where thickness in males was comparable. At thigh, the skin plus subcutaneous tissue thickness was more in females (P < 0.05), across all BMI ranges. At abdomen, thickness was more in females for the BMI ranges 17-19 kg/m(2) and 23-25 kg/m(2), while it was comparable across all other BMI ranges (P > 0.05). CONCLUSIONS: Skin and subcutaneous tissue thickness can be estimated by BMI. In general it is higher in females.

Barriers and solutions to diabetes management: An Indian perspective.

India, with one of the largest and most diverse populations of people living with diabetes, experiences significant barriers in successful diabetes care. Limitations in appropriate and timely use of insulin impede the achievement of good glycemic control. The current article aims to identify solutions to barriers in the effective use of insulin therapy viz. its efficacy and safety, impact on convenience and life-style and lack of awareness and education. Therapeutic modalities, which avoid placing an undue burden on patients' life-style, must be built. These should incorporate patient-centric paradigms of diabetes care, team-based approach for life-style modification and monitoring of patients' adherence to therapy. To address the issues in efficacy and safety, long-acting, flat profile basal insulin, which mimics physiological insulin and show fewer hypoglycemic events is needed. In addition, therapy must be linked to monitoring of blood glucose to enable effective use of insulin therapy. In conjunction, wide-ranging efforts must be made to remove negative perception of insulin therapy in the community. Patient- and physician - targeted programs to enhance awareness in various aspects of diabetes care must be initiated across all levels of health-care ensuring uniformity of information. To successfully address the challenges in facing diabetes care, partnerships between various stakeholders in the care process must be explored.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the West India cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from West India. RESULTS: A total of 4192 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 2846), insulin detemir (n = 596), insulin aspart (n = 517), basal insulin plus insulin aspart (n = 140) and other insulin combinations (n = 83). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 8.8%) and insulin user (mean HbA1c: 9.1%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -1.6%, insulin users: -1.7%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. CONCLUSION: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial.

BACKGROUND: Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve ß-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. METHODS: In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protégé study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0·5 U/kg per day and glycated haemoglobin A(1c) (HbA(1C)) of less than 6·5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697. FINDINGS: 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19·8% (41/207) in the 14-day full-dose group; 13·7% (14/102) in the 14-day low-dose group; 20·8% (22/106) in the 6-day full-dose group; and 20·4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0·03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group). INTERPRETATION: Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in ß-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children. FUNDING: MacroGenics, the Juvenile Diabetes Research Foundation, and Eli Lilly.