Indian Reality of Clinical Practice and Patient Profile in Diabetes Care: Lessons from the IMPACT survey

India shoulders a heavy burden of diabetes mellitus (DM), the management of which is suboptimal globally. Objectives: Insulin Management: Practical Aspects in Choice of Therapy (IMPACT) survey was designed to gain insight into the ground (in-clinic) reality of DM management by physicians in India. Methods: A survey consisting of 12 multiple-choice questions was conducted by SurveyMonkey ® , focusing on practice profile, patient profile, and other aspects of DM management. Results: The survey included 2424 physicians. Majority of them were general physicians (58.5%) followed by diabetologists (31.1%). Most (49.2%) of the respondents specified that the ideal time for a DM consultation is 15 min. However, 73.4% of them provided consultation of <10 min because of heavy patient load. Nearly half of the respondents reported that their patients consumed a diet with carbohydrate content of 60% to 80%, and 79.4% of them admitted that <50% of their patients adhered to dietary advice. About 73.5% of the respondents believed controlling fasting plasma glucose (FPG) level alone would not adequately control postprandial plasma glucose (PPG) level, and 93.0% of them preferred an insulin therapy at the initiation that controls both FPG and PPG levels. Conclusion: Limited consultation time, high-carbohydrate diet, and a need for choosing insulin regimens that provide control for both PPG and FPG levels are some ground realities of DM management in India. These realities need to be factored in while choosing treatment options to achieve the desired glycemic control and improve the status of diabetes care.

Histopathological study of adrenocortical masses with special references to Weiss score, Ki-67 index and p53 status.

Background: Adrenal mass present with wide morphological spectrum and clinical manifestation, which can give rise to diagnostic confusion. Proper categorization is essential for individualized treatment. Aim and Objective: (1) Application of Weiss criteria to differentiate between benign and malignant adrenocortical neoplasm (2) co-relation of Ki-67 and p53 expression with the Weiss score. Materials and Methods: A prospective, observational study was conducted in the Department of Pathology in collaboration with department of Endocrinology and Urology of a tertiary care hospital including 19 patients presented with clinically symptomatic or radiologically detected adrenocortical mass. Tissue for histopathological study was obtained in the form of the postoperative material. Histopathological categorization was done, and Weiss score was calculated in all tumors. Ki-67 and p53 immunohistochemistry were performed. Result: A total 19 cases of adrenal mass lesions were included. Cushing syndrome was the presenting symptoms in 26.3% adrenocortical masses. All patients with tumors with Weiss’s score <3 (Group 1) were alive after 24 months of followup compared to 20% of those with Weiss’s score >3 (Group 2). Statistically signifi cance difference was noted in average weights and size of the tumors. Distribution of Ki-67 and p53 expression between Group 1 and Group 2 were compared and found statistically highly signifi cant with Fisher’s two-tailed P < 0.001. Conclusion: The combination of the meticulous evaluation of clinical, morphological and immunohistochemical profi le helps in proper categorization of adrenocortical mass.

Occurrence of osteoporosis & factors determining bone mineral loss in young adults with Graves’ disease.

Background & objectives: There is a paucity of data with conflicting reports regarding the extent and pattern of bone mineral (BM) loss in Graves’ disease (GD), especially in young adults. Also, interpretation of BM data in Indians is limited by use of T-score cut-offs derived from Caucasians. This study was aimed to evaluate the occurrence of osteoporosis in active treatment naive patients with GD and determine the factors predicting BM loss, using standard T-scores from Caucasians and compare with the cut-offs proposed by the Indian Council of Medical Research (ICMR) for diagnosing osteoporosis in Indians. Methods: Patients with GD, >20 yr age without any history of use of anti-thyroid drugs, and normal controls without fracture history, drugs use or co-morbidities underwent BM density (BMD) assessment at lumbar spine, hip and forearm, thyroid function and calcium profile assessment. Women with menopause or premature ovarian insufficiency and men with androgen deficiency were excluded. Results: patients with GD (n=31) had significantly lower BMD at spine (1.01±0.10 vs. 1.13±0.16 g/cm2), hip (0.88±0.10 vs. 1.04±0.19 g/cm2) and forearm (0.46±0.04 vs. 0.59±0.09 g/cm2) compared with controls (n=30) (P<0.001). Nine (29%) and six (19.3%) patients with GD had osteoporosis as per T-score and ICMR criteria, respectively. None of GD patients had osteoporosis at hip or spine as per ICMR criteria. Serum T3 had strongest inverse correlation with BMD at spine, hip and femur. Step-wise linear regression analysis after adjusting for age, BMI and vitamin D showed T3 to be the best predictor of reduced BMD at spine, hip and forearm, followed by phosphate at forearm and 48 h I131 uptake for spine BMD in GD. Interpretation & conclusions: Osteoporosis at hip or spine is not a major problem in GD and more commonly involves forearm. Diagnostic criterion developed from Caucasians tends to overdiagnose osteoporosis in Indians. T3 elevation and phosphate are important predictors of BMD. Baseline I131 uptake may have some role in predicting BMD.

Serum vitamin-D predicts insulin resistance in individuals with prediabetes.

Background & objectives: Patients with diabetes and vitamin-D insufficiency have increased insulin resistance. Similar observations among individuals with prediabetes are not well documented. The aim of this study was to find the occurrence of vitamin-D insufficiency/deficiency among individuals with prediabetes and to evaluate the relationship between vitamin-D status and insulin resistance. Methods: One hundred fifty seven individuals with prediabetes who fulfilled all the inclusion and exclusion criteria underwent clinical examination, anthropometric measurements (waist circumference, waist-hip ratio, waist-height ratio) and blood sampling after overnight fast for estimation of fasting blood glucose, fasting insulin, 25(OH)vitamin-D, intact parathyroid hormone (iPTH) and lipid profile. One hour post 75 g glucose (1hPG) blood glucose during oral glucose tolerance test was measured. Results: Vitamin-D deficiency/insufficiency was found in 115 (73.25%) individuals with prediabetes. Severe vitamin-D deficiency (<10 ng/ml) was seen in 14.65 per cent individuals. Individuals with the lowest vitamin-D levels (<10 ng/ml) had the highest insulin resistance (HOMA2-IR: 2.04 ± 0.67). Serum 25(OH)D had a statistically significant inverse correlation with insulin resistance (HOMA2-IR; r=-0.33; P=0.008), and positive correlation with insulin sensitivity (QUICKI; r=0.39; P=0.002), after adjusting for BMI and HbA1c. There was no correlation between vitamin-D status and estimated beta cell mass (HOMA-β). The mean waist-height ratio among individuals with prediabetes was 0.57 (normal<0.5) indicating a high risk of cardiovascular morbidity. Individuals with elevated 1hPG>155 mg/dl had significantly higher BMI and worse insulin resistance, and 1hPG correlated well with 2 hour post glucose blood glucose (r=0.57; P<0.001). Interpretations & conclusions: Vitamin-D deficiency/insufficiency may have some role in the development/worsening of insulin resistance in individuals with prediabetes in our country who have a high cardiovascular risk. Prospective studies on a large group of individuals need to be done to confirm the findings.

Prevalence of diabetes and impaired fasting glucose in a selected population with special reference to influence of family history and anthropometric measurements--the Kolkata policeman study.

AIMS AND OBJECTIVES: The aim of this study was to estimate the prevalence of diabetes as well as IFG in a population of policemen and to evaluate the possible influence of some risk factors. MATERIAL AND METHODS: It was an epidemiological study on a group of policemen in Kolkata. Diagnosis of diabetes was based on history and fasting plasma glucose. The study population was divided in three categories: normoglycaemic, IFG and diabetes. BMI, waist circumference, WHR and waist-to-height ratio were estimated. RESULTS: Out of 2160 subjects with a mean age of 36.4 yrs (between 20 and 60 yrs), diabetes was found in 11.5% (10.4% known and 1.1% newly diagnosed) and 6.2% had IFG. Prevalence of diabetes was found to be increasing with age (p < 0.001). There was no statistically significant difference in BMI when compared between groups (normoglycaemic, IFG and diabetes). Waist circumference, waist-to-height ratio and WHR of normoglycaemic group were significantly less than those with IFG and diabetes; however there was no statistically significant difference between the diabetes and IFG groups. Parental history had significant influence on the prevalence of diabetes; a 37.5% prevalence was found in persons with history of biparental diabetes and 20.8% with uniparental diabetes, whereas it was only 9.9% without any family history (p < 0.01 and p < 0.05, respectively.). CONCLUSION: The prevalence of diabetes in the study population was high and was strongly influenced by family history, age and abdominal adiposity, without having any appreciable impact of BMI.

Atorvastatin improves arterial stiffness in normotensive normolipidaemic persons with type 2 diabetes.

Increased arterial stiffness is an independent predictor of cardiovascular disease and mortality in middle-aged and olderadults. We measured arterial stiffness by pulse wave velocity (PWV)in brachial-ankle segments by automated oscillometry in 71 normotensive and normolipidaemic subjects with type 2 diabetes (40 males and 31 females). 57 patients (whose baPWV was more than 1400 cm/second) were randomised into two groups, group A (n=29) were given 10 mg atorvastatin daily for 6 months and group B (n=28) were given placebo. After 6 months, atorvastatin group had significant improvement in brachial-ankle pulse wave velocity (baPWV) (1712.03 +/- 349.9 cm/second versus 1558.81 +/- 303.26 cm/ second, p< 0.05). Though the placebo group showed some improvement (1692.03 +/- 425.15 cm/second versus 1636.78 +/- 425.1 cm/second) it was not statistically significant. Despite correlation was noted between baPWV and systolic blood pressure (SBP), there was no significant correlation between the mean baPWV and duration of diabetes, body mass index (BMI), waist circumference, waist-hip ratio (WHR), waist to height ratio (WHtR), glycated haemoglobin (HbA1c), LDL, HDL cholesterol and spot urine albumin creatinine ratio (ACR) at the baseline. The decrement of LDL-cholesterol is correlated with the decrement of the baPWV in the atorvastatin group only (p<0.01).

A study of aspirin resistance in type 2 diabetes.

Aspirin is currently known to give inadequate protection against coronary artery disease in diabetes compared to person without it. We evaluated 97 consecutive patients with type 2 diabetes for assessing laboratory aspirin resistance and attempted to assess the impact of various clinical and biochemical parameters on it. Thirty-eight patients (39.1%) were found to be less sensitive to the action of aspirin, 7 persons (7.2%) were found to be resistant and 31 persons (31.9%) were aspirin semi-responders. Only total cholesterol, LDL-cholesterol and triglyceride had statistically significant impact on aspirin resistance (p<0.05). Three persons out of 9 with some form of macrovascular disease had aspirin resistance.

A study on endocrine changes in patients in intensive care unit.

Pattern of endocrine changes in moderate to severely ill patients in a medical intensive care unit, correlation with the severity of illness and whether these changes can predict outcome of the critically ill patients were evaluated and studied in 80 patients admitted with acute physiology and chronic health evaluation (APACHE) II score >10 and without any pre-existing endocrinopathies or on drugs likely to affect the endocrine axis. Adrenal insufficiency was present in 45%, and mortality was higher in those with lower (<15 microg/dl) and higher (>30 microg/dl) serum cortisol. Sick euthyroid syndrome was detected in 80%, and those with low mean T3 (<0.6 ng/ml), free T4 (<0.89 ng/dl) and total T4 (<4 microg/dl) and had increased mortality. Hypotestosteronaemia was found in 92% of men and was significantly associated with severity of illness in men. Though prolactin is the first hormone to be elevated, there was no correlation between prolactin and severity of illness or mortality.

Early treatment with low fixed dose (5 mCi) radioiodine therapy is effective in Indian subjects with Graves' disease.

There is little consensus regarding the most appropriate dosage regimen for radioiodine treatment in Graves' disease. The authors evaluated the efficacy of low fixed dose (5mCi) of radioiodine therapy, in terms of its cure rate and promptness of control, as well possible factors influencing the outcome. One hundred and twenty five consecutive patients with Graves' disease with persistent disease activity despite receiving carbimazole were treated with 5 mCi fixed dose of I131. Patients, who remained hyperthyroid at 1 year, received a second dose of 7.5 mCi of I113. After first dose 73.6% were cured (36.8% hypothyroid and 36.8% euthyroid), while 26.4% patients did not respond. Those who achieved cure had significantly lesser goiter size (84.6% with grade I goiter and 70.7% with grade II) and had received significantly shorter duration of prior carbimazole therapy (22 +/- 10 months versus 63 +/- 27 months) (p < 0.01). Age, sex, baseline T3, T4, 24 hour I131 uptake did not affect the cure rate. Mean time to response was 7 +/- 4 months. One hundred and three (82.4%) patients were cured after 2 doses while only 22 (17.6%) were nonresponsive. Hence, low fixed dose (5mCi) radio active iodine (RAI) therapy seems to be effective in Graves' disease particularly in patients with small sized goiter and short duration of pretherapy with thionamides.

Profile of hypopituitarism in a tertiary care hospital of eastern India--is quality of life different in patients with growth hormone deficiency?

Hypopituitarism is of diverse aetiology. Apart from pituitary adenoma and Sheehan's syndrome, snakebite is a common aetiology of hypopituitarism. A total of 82 patients of hypopituitarism were studied. Biochemical and radiological investigations were done in all the cases. A quality of life questionnaire was put among the patients. Scores were calculated from the answers of the questionnaire and they were assessed about quality of life. Though growth hormone deficiency is associated with poor quality of life there were no significant differences with patients with hypopituitarism without any growth hormone deficiency.

The thyroid nodule--evaluation and management.

Thyroid nodules are common; with the growing availability of sensitive TSH assays, fine needle aspiration biopsy (FNAB) and high resolution ultrasonography (HRUSG), thyroid nodules are being increasingly recognised, diagnosed and treated. The diagnosis of a thyroid nodule is associated with considerable anxiety for the patient; a systematic approach, by excluding the possibility of malignancy, helps allay such anxiety. Nodules are sometimes picked up on neck imaging for non-thyroid conditions; these so-called 'incidentalomas' also need evaluation to rule out malignancy. A sensitive TSH assay is usually the first investigation; a suppressed TSH level leading to a radionuclide scan and an FT4 level to detect toxic nodules that are best managed by radio-iodine or surgical ablation. Thyroid peroxidase antibody is estimated if the TSH level is high. Palpable nodules in euthyroid subjects are best evaluated by HRUSG followed by USG-guided FNA. For nodules <10 mm size, USG-guided FNA is recommended only if clinical or USG features are suspicious. While the benign nodules are kept under regular follow-up, all malignant nodules should be removed surgically. Cystic thyroid lesions are well managed by percutaneous ethanol ablation. Routine measurement of serum calcitonin and other sub cellular markers is not recommended.

Drug therapy in prediabetes.

Patients with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have been designated by American Diabetes Association (ADA, 2004) as having 'prediabetes', which indicates the higher risk of developing the disease in these patients. Prediabetes is important to recognise because of at least 2 major implications: increased risk for future diabetes and for atherosclerotic cardiovascular diseases. Pharmacotherapy in prediabetes should therefore be directed at preventing or, at least, delaying the onset of the disease as well as reducing the morbidity and mortality from atherosclerotic complications. Several drugs having different mechanisms of action, such as metformin, glitazones, acarbose, orlistat, nateglinide, glicazide, angiotensin-converting enzymes, angiotensin receptor blockers have been found to be effective in prediabetes to improve the glycaemic status, though they are still not recommended by any professional organisation.

Growth hormone deficiency in children: an approach to a child with short stature.

The importance of recognition of short stature in a child is very important as it allows one to identify important medical conditions where physical shortness is only one manifestation. Causes of short stature are: Familial, idiopathic, delay in growth and maturation, chronic systemic illnesses, endocrinopathies, rickets, skeletal dysplasia, chromosomal disorders and emotional deprivation. Proper history, physical examination, endocrine and non-endocrine investigations are crucial for arriving at the diagnosis of short stature. The cardinal manifestation of growth hormone deficiency in children obviously interferes physical growth. Causes of growth hormone deficiency may be congenital or acquired. A peak growth hormone level of < 10 microg/l in response to stimulation tests along with some clinical features is generally considered sufficient to diagnose growth hormone deficiency. Growth hormone in a dose of 25-50 microg/kg/day should be administered subcutaneously once daily at bed time for growth hormone deficiency state.

Fine needle aspiration cytology of thyroid gland and histopathological correlation--revisited.

Fine needle aspiration of the thyroid gland, followed by cytological studies and their correlation with histopathological diagnosis have been undertaken to assess the effectiveness of fine needle aspiration cytology in diagnosing disorders of this gland. The cases in which discrepancies had arisen between these two methods of diagnosis have also been reviewed. Out of the total 100 patients studied, 28 were cases of simple colloid goitre, 17 of adenomatoid goitre, 10 of autoimmune thyroiditis ranging from lymphocytic thyroiditis to Hashimoto's thyroiditis, 28 of follicular neoplasia, 10 of papillary carcinoma, one of medullary carcinoma, 2 of anaplastic carcinoma and 4 of cystic lesions of the thyroid gland. Although, fine needle aspiration cytology of the thyroid gland was diagnostic in 75% of cases, it did not correlate with the histopathological diagnosis in the remaining 25% of cases. Possible reasons behind these discrepancies have been discussed.

Rational choice of oral antihyperglycaemic agents.

Until 1995 sulphonylureas and metformin formed the mainstay of oral pharmacotherapy of type 2 diabetes mellitus. Since then many new insulin secretagogues and new classes of oral antihyperglycaemic agents have been launched. This has improved the management of type 2 diabetes mellitus. Oral agents available currently in Indian market are: Those predominantly targeting beta cell dysfunction, those predominantly targeting insulin resistance and those inhibit carbohydrate absorption. Strategies for treatment with oral antihyperglycaemic agents are: Targeting fasting hyperglycaemia, targeting postprandial hyperglycaemia, minimising cost therapy, minimising weight gain and minimising patient effort strategies. Special situations where antihyperglycaemic agents used are: Teenage diabetes, elderly diabetes, persons with erratic lifestyle, persons with cardiac disease, renal disease and in pregnancy.