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.

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.

Baseline results indicate poor glycemic control and delay in initiation and optimization of insulin therapy: results from the improving management practices and clinical outcomes in type 2 diabetes study.

INTRODUCTION: 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 patients with type 2 diabetes. MATERIALS AND METHODS: A total of 20,653 patients from 885 centers across India were enrolled and treated with premixed insulin therapy as per IIG or routine care. RESULTS: Most of the participating centers (81.7%) reported following a diabetes guideline in their practice routinely but only 20.4% targeted HbA1c <7%. Very few of the physicians (2.7%) reported that most of their patients (>75%) achieved an HbA1c <7%. Most of the physicians (39.8%) also agreed that only 10-25% of the patients agree to start insulin therapy at the first counseling. Mean duration of diabetes before initiating insulin in patients using oral anti-diabetic drugs (OADs) was 7 years, indicating a delay in initiating insulin therapy. The difference in mean daily dose of insulin at initiation vs. at 26 weeks was only 0.8 U (25.8 ± 11.3 at initiation compared to 26.6 ± 9.5, respectively, p = ns) suggesting lack of treatment optimization. Weekly titration till achieving HbA1c <7% was done in 51.1% of the patients and only 8.9% performed self-titration. CONCLUSION: Baseline glycemic control in these patients was poor and reflects a delay in initiating insulin therapy. Data also reflect a lack of optimization of insulin doses.

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.

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.

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.

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.

Hypertension in diabetes.

Diabetes mellitus and hypertension are both major public health problems in our country, which co-exist frequently resulting in significant morbidity and mortality. The reported prevalence of hypertension in diabetes varies widely but is probably 1.5-2 times higher than that reported in the general population. In type 2 diabetics many are hypertensives at the time of diagnosis, while in type 1 diabetes, hypertension is predominantly associated with the development of nephropathy. Hypertension in diabetes is due to several pathophysiological mechanisms which include increased volume expansion, altered sodium homeostasis, increased peripheral vascular resistance, hyperinsulinaemia, insulin resistance, etc. The presence of hypertension in diabetic patients increases the mortality 4-5 folds, largely through coronary artery disease and stroke. It may also be an aetiological factor in the development of nephropathy and retinopathy. Treatment of hypertension in a diabetic has considerable therapeutic advantages and should be carried out vigorously. Lifestyle modifications have a useful role in the treatment of mild hypertension and have a beneficial effect on other cardiovascular risk factors. The choice of antihypertensive agents should be based on their potential impact on the metabolic abnormalities observed in diabetics. Amongst the currently available antihypertensive agents, ACE inhibitors and calcium channel blockers are the favoured agents.

Lifestyle modification in management of diabetes mellitus.

India has the largest diabetic population in the world. Change in eating habits, increasing weight and decreased physical activity are major factors leading to increased incidence of type 2 diabetes. Obesity is the most important modifiable risk factor. Smoking is an independent risk factor for type 2 diabetes mellitus. Diet and exercise are primary therapeutic options for its management. Dietary management should not only aim to achieve glycaemic control but to normalise dyslipidaemia. Smoking cessation reduces the risk of morbidity and mortality in CAD. Exercise improves the condition of a diabetic patient. Exercise includes yoga practices which have a role to play in the prevention of type 2 diabetes.

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.

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.

Diet and lifestyle guidelines and desirable levels of risk factors for the prevention of diabetes and its vascular complications in Indians: a scientific statement of The International College of Nutrition. Indian Consensus Group for the Prevention of Diabetes.

BACKGROUND: There has been a rapid increase in the prevalence of diabetes and cardiovascular disease in India, in association with rapid changes in diet and lifestyle. In adults, the prevalence of diabetes, hypertension and coronary artery disease is two- to threefold greater in the urban population than in rural populations; it is associated with modest insulin resistance in urban groups. METHODS: In response to a proposal by the International College of Nutrition that specialist experts should develop consensus recommendations for the prevention of chronic diseases, Indian specialists in diabetes and vascular disease have collaborated to produce guidelines relevant to the population of India. RECOMMENDATIONS: Because Indian urban populations have a modest increase in overweight and low rates of obesity in association with the rapid emergence of diabetes and cardiovascular risk, a body mass index of 21 kg/m2 should be considered safe, with a range of 19-23 kg/m2 acceptable; > 23 kg/m2 should be considered overweight, and > 25 kg/m2 should be taken to indicate obesity. A waist:hip ratio > 0.88 in males and > 0.85 in females should be considered to indicate central obesity, because the prevalence of coronary disease, hypertension and associated disturbances of insulin resistance are more common above these limits. For the prevention of vascular disease, there is general international consensus that the desirable serum concentration of cholesterol should be < 170 mg/dl (> 4.42 mmol/l), which may also be optimal for Indians; values between 170 and 200 mg/dl (4.42-5.2 mmol/l) should be considered borderline. The critical values for low density lipoprotein cholesterol may be < 90 mg/dl (ideal), 90-110 mg/dl (borderline high) and > 110 mg/dl (high) (< 2.32, 2.32-2.84 and > 2.84 mmol/l, respectively). Fasting triglycerides should be < 150 mg/dl (< 1.69 mmol/l) and high-density lipoprotein cholesterol > 35 mg/dl (> 0.9 mmol/l). The limit for the total energy derived from fat intake should be < 21%/day (7% each for saturated, polyunsaturated and mono-unsaturated fatty acids). The carbohydrate intake should provide more than 65% of daily energy, mainly from complex carbohydrates. A daily dietary intake of 400 g fruits, vegetables and legumes, 400 g cereals, in conjunction with 25 g soya bean or mustard or canola oils (rich in n-3 fatty acids) in place of fats rich in saturated fat, may be protective against diabetes and vascular disease. Moderate physical activity with the aim of burning 300 Kcal/day (> 1255 KJ/day), and cessation of tobacco and alcohol consumption, may provide an effective programme for prevention of diabetes and its vascular complications in Indians.

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.

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.