Type 2 Diabetes and Precursors in Community Dwelling Asian Indian Adult Youth.

Background: Recent studies have shown a high prevalence of Type-2-diabetes (T2DM) (24%) and prediabetes (18.1%) in Kerala. There is no community based study from South Asia regarding the prevalence of type 2 diabetes and its precursors in the young adult population. This community based study was done to find the prevalence of type 2 diabetes and its precursors in South Indian adult youth (18-30 years age) of Thiruvananthapuram district. Research Design and Methods: Cross sectional design was used for this study. Multistage cluster sampling was used to enrol community dwelling youth of 18 to 30 years, residing in Thiruvananthapuram district. Six panchayath wards from rural and urban regions and 4 from coastal area were randomly selected as the primary sampling units. Trained staff nurses conducted the survey with the help of accredited-social-health-activists (ASHA). Socio-demographic data, anthropometry, clinical features of insulin resistance, and random capillary glucose (CG) and blood pressure were assessed and recorded. Oral Glucose tolerance test or HbA1c was done for participants with a CG ≥130 mg/dl for diagnosis of diabetes and prediabetes. Results: A total of 1031 participants were included from the rural (n = 394), coastal (n = 269) and urban (n = 368) areas. Prevalence of hyperglycaemia i.e., T2DM and pre-diabetes was 0.48% (n = 5) and 2.4% (n = 25) respectively. Family-history of T2DM was present in 35.1% subjects. Prevalence of overweight, obesity and abdominal-obesity was 28.2%, 16.1% and 28.4% respectively. Clinical-features of insulin resistance (CFIR) were present in 27.1% subjects (acanthosis [17.7%], skin tags [1.7%] and PCOS phenotype [10.7%]). Among various anthropometric measurements and their derivatives, CFIR correlated best (r = 0.24, P < 0.01) with the product of BMI and the sum of abdominal circumference and hip circumference (Trivandrum Medical College [TMC] -adiposity-index), which is a newly proposed parameter. Hyperglycaemia was more common in males, did not correlate with waist hip ratio, and correlated best again with TMC-adiposity-index ((r = 0.13, P < 0.01). Conclusions: The burden of insulin resistance in the young South Indian population, hitherto unknown in any community based study, has been studied for the first time. The prevalence of precursors of T2DM is high in this population. Early identification of 'at risk' individuals could provide a window of opportunity for preventing or delaying future diabetes and its long term complications. TMC adiposity index could become a valuable tool in the anthropometric assessment for predicting future T2DM.

Reference range for glycated haemoglobin in full term non diabetic pregnant women: a multicentric cross sectional study.

BACKGROUND: There are no large studies to define the normal value of glycated haemoglobin (HbA1c) measured in full term pregnant women measured at the time of delivery. RESEARCH DESIGN AND METHODS: The study was conducted at three government hospitals in South India. Clinical data, maternal blood sample and foetal cord blood sample were collected from women admitted for safe confinement. Mean (± SD) of HbA1c in participants with no known diabetes (gestational or pregestational) or any complications (maternal or fetal) is described, 2.5th-97.5th centile reference range was derived. RESULTS: From 3 centres, 2004 women participated in the study. Data from 1039 participants who had no history of diabetes or any maternal or fetal complication were used to determine the reference range for HbA1c at term pregnancy. The mean HbA1c in subjects devoid of diabetes and its known complications was 5.0 (± 0.39) %. The reference range for normal HbA1c at term in these women was found to be 4.3-5.9%. Maternal HbA1c at term pregnancy in non-diabetic pregnant women is associated with pre-pregnancy BMI, maternal age and 2-h plasma glucose level of 2nd trimester oral glucose tolerance test (OGTT). CONCLUSIONS: The mean HbA1c at term pregnancy in non-diabetic women admitted for safe confinement is 5.00 (± 0.39) %. An HbA1c of 5.9% or more at term should be considered abnormal and women with such a value may be kept at a close surveillance for development of diabetes.

Lipid Profile in Indian Patients With Type 2 Diabetes: The Scope for Atherosclerotic Cardiovascular Disease Risk Reduction.

OBJECTIVE: Reduction of atherosclerotic cardiovascular disease (ASCVD) risk in patients with diabetes requires proper management of lipid parameters. This study aimed to find the pattern of dyslipidemia and scope of ASCVD risk reduction in patients with diabetes by lipid management. METHODS: Clinical, biochemical, and medication profiles of all patients with diabetes attending a tertiary diabetes care hospital over a 2-year period were collected. The prevalence of various lipid abnormalities was determined after excluding patients with thyroid dysfunction and those on lipid-lowering medications. Patients were stratified according to LDL cholesterol, HDL cholesterol, and triglyceride levels, and other clinical parameters were compared among the groups. The adequacy of statin treatment was assessed based on American Diabetes Association guidelines. RESULTS: Nine hundred and seventy-one patients were included. The prevalence of hyperlipidemia was 40.0%, of whom 14.6% were newly diagnosed. The most common lipid abnormality was elevated LDL cholesterol. Higher A1C and fasting blood glucose values were found to be associated with higher LDL cholesterol levels. Twenty-seven percent of patients with indications for treatment with statins were receiving them. Of those being treated with statins, 42.6% had an LDL cholesterol level ≥100 mg/dL. CONCLUSION: In South Indian patients with type 2 diabetes and fair glycemic control, high LDL cholesterol is the predominant lipid abnormality. There remains a huge potential for ASCVD risk reduction in this population if the knowledge practice gap is addressed.

Incidence of New-Onset Diabetes and PostTransplant Metabolic Syndrome after Liver Transplantation - A Prospective Study from South India.

BACKGROUND AND AIMS: Liver transplantation has become an effective therapy for patients with end-stage liver disease. The risk of new-onset diabetes after transplantation (NODAT) and posttransplant metabolic syndrome (PTMS) is high among patients after liver transplantation. These are thought to be associated with increased risks of graft rejection, infection, cardiovascular disease, and death. Our study aimed to document the incidence of NODAT and PTMS and analyze pre and posttransplant predictive factors for their development in patients undergoing a liver transplant. METHODS: This was a prospective comparative study on 51 patients who underwent live donor liver transplantation. They were evaluated at baseline, 3 and 6 months after transplantation with fasting glucose, lipids, serum insulin levels, C-peptide, and HbA1C. They were followed up at 5 years to document any cardiovascular events or rejection. RESULTS: The incidence of preoperative diabetes mellitus (DM) in the study group was 25/51 (49%). The incidence of NODAT was 38.5% (10/26 patients) and PTMS 29% (10/35), respectively. Age (47.7 ± 5.4 vs 41.5 ± 12.7 years), HOMA2 - IR (2.3 ± 1.8 vs 2.1 ± 1.6), serum insulin (16.1 ± 12.0 vs 17.9 ± 14.5), and C-peptide (4.6 ± 0.5 vs 4.8 ± 0.7) were similar at baseline in the NODAT group compared to those who did not develop it. Mean tacrolimus levels were higher in PTMS group (6.8 ± 2.9 vs 5.0. ± 2.0 P value = 0.042). By the end of 5 years, 7 patients expired; 6 due to rejection and one due to cardiovascular disease. Moreover, 2 of these patients had preexisting DM and 2 had NODAT. CONCLUSIONS: None of the baseline metabolic factors in patients undergoing liver transplant were predictive of the development of NODAT or PTMS. Mean tacrolimus levels were significantly higher in the PTMS group. A 5-year follow-up showed no excess risk of cardiovascular events or rejection in those with preexisting DM or in those who developed NODAT.

Prevalence and Associations of Hypothyroidism in Indian Patients with Type 2 Diabetes Mellitus.

Both type 2 diabetes and hypothyroidism are highly prevalent disorders in the community. The existing data regarding prevalence of hypothyroidism in patients with diabetes comes mostly from small studies. There are only two studies with a sample size of more than 1000 diabetic patients, none of which have been done in South Asians. The present study evaluated patients with type 2 diabetes for presence of hypothyroidism and the clinical factors associated with it. The demographic, anthropometric, clinical, and biochemical parameters of consecutively enrolled patients with diabetes were systematically collected and analyzed. A total of 1152 middle aged patients with type 2 diabetes with a mean duration of diabetes of around 10 years were enrolled. Nearly 40 percent of the patients were obese and overweight, respectively, for South Asian standards and abdominal obesity was seen in around 90% patients. Clinical hypothyroidism (TSH>10 mIU/ml) was present in 113 of patients (9.83%) and another 68 patients (5.9%) had subclinical hypothyroidism (TSH 5-10 mIU/ml). Anemia (odds ratio : 2.19), overweight/obese status (odds ratio 2.07), and known dyslipidemia (odds ratio : 1.99) were found to have independent association with clinical hypothyroidism. HbA1c, abdominal obesity, poor control of hypertension, lipid parameters, microalbuminuria, and renal dysfunction showed no difference among patients with hypothyroidism when compared with euthyroid patients. Subclinical hypothyroid patients had no difference in any of the above analyzed parameters when compared to the euthyroid patients. This study shows that a significant proportion of type 2 diabetes patients suffer from clinical or subclinical hypothyroidism and screening for the same may be appropriate.

A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus.

AIM: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA) of foot in terms of clinical and radiological parameters. MATERIAL AND METHODS: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC). Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1°F. RESULTS: Among the 40 patients, 30 (75%) had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate) was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. CONCLUSION: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. (99m)Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

Foot care practice - the key to prevent diabetic foot ulcers in India.

BACKGROUND: The magnitude of diabetic foot ulcers (DFUs) and the amputation rates due to DFUs remain high even in developing and developed countries. Yet, the influence of knowledge, attitude, and practice (KAP) of diabetic foot care (DFC) on DFU incidence is not studied much. OBJECTIVE: To study causal relationship between knowledge, attitude and practice (KAP) on DFC between diabetic patients with and without DFUs; and the risk factors associated with DFUs. METHODS: A consecutive of 203 diabetic patients (103 with DFU and 100 without DFU) were included in the study. Their demographic details, medical history, and personal habits were recorded. KAP on DFC was assessed using a questionnaire. Responses were recorded, scored, and analyzed. RESULTS: Of the cohort, 67.5% were males, mean age: 59.9 ± 11.4 years. Patients without DFU had good knowledge on DFC compared to those with DFU (86% versus 69.9%) (p<0.001). Incidence of DFU was 9% and 39.8% (p<0.001) among patients who practiced and not practiced DFC respectively. 88% patients with and without DFUs; showed favorable attitude toward adopting DFC. Risk factors - diabetic peripheral neuropathy, peripheral vascular disease, retinopathy, nephropathy, smoking, tobacco chewing and alcohol consumption were significantly (p<0.001) associated with DFUs. CONCLUSIONS: An inverse relationship between DFU and foot care knowledge as well as practice was observed. Apart from tight glycemic control, diabetic patients must be educated and motivated on proper foot care practice and life style modifications for preventing DFUs.

Geriatric thyroidology: An update.

Thyroid anatomy and physiology change in the elderly with age-related fibrosis and atrophy in the thyroid gland and changes in thyroid hormones. The incidence of thyroid nodules increases with age, making the thyroid more nodular. Hypothyroidism is common in the elderly and, if untreated, is associated with significant morbidity. Elderly patients are sensitive to iatrogenic hyperthyroidism, especially with preexisting cardiac disease. Hence, treatment of hypothyroidism should be individualized and should be started with low doses and titrated according to response. Hyperthyroidism, although less common in the elderly if present, is associated with significant cardiac morbidity and mortality. Radioiodine therapy is considered a safe primary treatment in the elderly with hyperthyroidism. Management of subclinical hypo- and hyperthyroidism is still controversial. The incidence of thyroid tumors increase with age. Thyroid malignancy in the elderly is considered as a more advanced disease compared with the young, and aggressive management is recommended.

Targeted treatment of invasive fungal infections accelerates healing of foot wounds in patients with Type 2 diabetes.

AIM: To test the hypothesis that fluconazole plus standard care is superior to the standard care for diabetic foot wounds infected with deep-seated fungal infections. METHODS: We carried out a randomized, controlled, open-label, parallel-arm study in 75 patients with both fungal and bacterial infections in deep tissues of diabetic foot wounds. Thirty-seven patients (control group) were given standard care (surgical debridement + culture-specific antibiotics + offloading + glycaemic control) and 38 patients (treatment group) were given fluconazole 150 mg daily plus standard care. Wound surface area was measured every 2 weeks until the endpoints (complete epithelialization or skin grafting) were met. RESULTS: By week 4, the mean wound surface area reduced to 27.3 from 111.5 cm(2) in the treatment group, as opposed to 67.1 from 87.3 cm(2) in the control group. Subsequently, the mean wound surface areas were remarkably smaller in the treatment group compared with the control group, and statistically significant differences (P ≤ 0.05) in mean wound surface area were observed between the treatment group and the control group at week 6. However, no statistically significant (P ≤ 0.47) difference in complete healing was observed between the treatment group and the control group, 20 vs. 24. The mean wound healing time for the treatment group was 7.3 weeks, whereas for the control group it was 11.3 weeks (P ≤ 0.022). Similarly, the probability of wound healing in the treatment group was 50 vs. 20% in the control group at week 10. CONCLUSIONS: Fluconazole plus standard care was superior to standard care alone in accelerating wound reduction among patients with diabetes with deep-seated fungal infections in diabetic foot wounds. Those in the treatment group who did heal, healed more quickly (P ≤ 0.022), but overall healing was not different.

Turner syndrome and its variants.

Case records of female patients with karyotype proven turner syndrome were analyzed. 11 patients had classic Turner karyotype (Group 1) and 13 patients had karyotype suggestive of one of the variants of Turner syndrome (Group 2). There was a median difference of 3 years between the age of presentation and the age of diagnosis in Group 2. Out of the thirteen patients in Group 2, 4 had no clinical stigmata of Turner Syndrome; the rest (n=9) had one or more of the typical clinical stigmata of Turner Syndrome. One patient with a complex mosaic karyotype also had an intracranial medulloblastoma. One patient in each group had coarctation of the aorta. 5 patients in Group 1 and 3 patients in Group 2 had primary hypothyroidism and received levothyroxine. The median Thyroid Stimulating Hormone levels were significantly higher among patients in group 1 than in group 2.

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator (AIRE) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1-7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.

High prevalence of undetected thyroid disorders in an iodine sufficient adult south Indian population.

India is in the transition phase from iodine deficiency to iodine sufficiency, and this is expected to change the thyroid status of the population. The thyroid status and auto-immune status of adult Indian population in the postiodisation phase is largelyunknown, and this study was conducted to answer this question. A cross-sectional population survey was conducted in two phases among the residents of urban coastal area of central Kerala. The initial phase included a house-to-house survey of 3069 adults (>18 years of age), selected by cluster sampling method. From the surveyed population, 986 subjects underwent further physical examination and biochemical evaluation for thyroid function, thyroid autoimmunity status and iodine status. The total prevalence of goitre was 12.2% and median urine iodine excretion was 211.4 mcg/l (mean 220.3 +/- 99.5 mcg/l) indicating iodine sufficiency. Thyroid function abnormalities were present in 19.6% of subjects. Subclinical hypothyroidism was present in 9.4%. Among the population with normal thyroid function, 9.5% and 8.5% respectively had positive anti-TPO and anti-TG antibodies. Among those with thyroid dysfunction, 46.3% had positive anti-TPO and 26.8% were anti-TG positive. A significant proportion of this iodine-sufficient adult population had thyroid disorders. Further studies are required to characterise the reasons for this high prevalence. Iodine deficiency as well as thyroid dysfunction should both be the focus of public health strategies in susceptible populations.

Glycaemic status and prevalence of comorbid conditions among people with diabetes in Kerala.

BACKGROUND: We aimed to assess the glycaemic status and prevalence of comorbid conditions such as obesity, hypertension and dyslipidaemia in people with diabetes in a southern Indian community. METHODS: A cross-sectional community survey of adults > 18 years of age was done in central Kerala. Among the 3069 subjects surveyed, 276 were known to have diabetes. Of these, 169 who had type 2 diabetes underwent a detailed physical examination and anthropometric measurements, and determination of levels of fasting blood glucose, glycosylated haemoglobin, fasting lipid, serum creatinine and urine protein. Data of 164 subjects who had glycosylated haemoglobin levels were included for final analysis. RESULTS: The mean (SD) duration of diabetes was 5.5 (5.04) years and the mean age was 56.9 (11.4) years. Among the patients, 28 (17.2%) were receiving no treatment for diabetes, 24 (14.7%) were on diet control and 111 (68%) on pharmacotherapy. Only 6 patients were on insulin. The mean fasting blood glucose was 153 (63) mg/dl and the mean glycosylated haemoglobin level was 8.1 (2.34)%. In 60% of patients, the glycosylated haemoglobin level was above the recommended target of 7%. Obesity (31%), hypertension (51%), low-density lipoprotein cholesterol > 100 mg/dl (90%) and serum triglyceride levels > 150 mg/ dl (38%) were present in the study population. Only 29% of patients were on antihypertensive treatment and 5% on lipid-lowering agents. CONCLUSION: In this population, only 40% of people with diabetes had adequate glycaemic control. The use of insulin was infrequent. Comorbid conditions were common and inadequately treated. This indicates a lack of proper diabetic care in this community, which could lead to an increase in the burden of cardiovascular disease in the future.

Type 1 diabetes versus type 2 diabetes with onset in persons younger than 20 years of age.

Type 1 diabetes (T1D) is the most common form of diabetes in children in Western countries. There have been no large studies of childhood diabetes from India. We undertook the MEDI study (Multicenter Survey of Early Onset Diabetes in India) to assess the proportion of various subtypes of diabetes among the young subjects presenting to the endocrinology divisions of seven large teaching hospitals in different regions of India. In addition, we compared the clinical features of T1D and type 2 diabetes (T2D) in Indian subjects. Patients with onset of disease at younger than 20 years of age were included in this study. Six hundred and three subjects (603) were studied of whom 535 subjects (89%) had T1D, 36 (6%) had T2D, 18 (3%) had diabetes related to tropical pancreatitis or other forms of chronic pancreatitis, while other subtypes accounted for the rest. Compared to those with T2D, subjects with T1D were younger, had a lower C-peptide level, higher prevalence of ketosis, lower prevalence of acanthosis nigricans, and lower LDL and triglyceride levels. When compared with that of T2D, a higher proportion of patients with T1D were positive for GAD-65 and IA-2 antibodies, and this difference was statistically significant for GAD-65 antibodies. Overall, this large multicenter study showed that T1D is the commonest form of diabetes in childhood. T2D is the next most common kind, while chronic pancreatitis-related diabetes is uncommon.

Acanthosis Nigricans and insulin levels in a south Indian population-(ADEPS paper 2).

OBJECTIVE: Aim of the study was to determine the prevalence of Acanthosis Nigricans (AN) in a central Kerala south Indian population and to evaluate its correlations with diabetes, obesity, insulin levels and other factors. METHODS: A cross-sectional community survey including physical examination and biochemical evaluation was conducted among adults above the age of 18 years in central Kerala In the first phase of the study 3069 participants were surveyed using questionnaires regarding socioeconomic status and medical details. Among them 986 subjects were evaluated in the second phase of the study which included anthropometric measurements, examination for blood pressure and Acanthosis Nigricans, blood tests such as blood glucose, fasting lipids. Fasting serum insulin level was measured for all non-diabetic subjects. Statistical analysis was done using SPSS 11.0 version software. RESULTS: RESULTS of the study showed that 16.1% of population had AN and it was significantly higher among females (19.6%) than males (11.4%). Prevalence of AN was highest in 30-40 year age group and it decreased with the age. Prevalence of AN correlated positively with female gender, obesity, high triglyceride levels and presence of diabetes. Presence of AN was significantly associated with higher fasting insulin levels. Males with AN had significantly higher insulin values than females with AN. CONCLUSION: AN has stronger clinical relevance among males than females and it can be used as a marker of insulin resistance in south Indian population especially if obesity and family history of diabetes are also present.

Audit of care of patients with congenital adrenal hyperplasia due to 21-Hydroxylase deficiency in a referral hospital in South India.

We carried out an audit of management of patients with 21-Hydroxylase deficiency CAH who presented to the Department of Endocrinology OPD from 1999 till 2004 and had a minimum follow up of 6 months. Of the 30 patients analysed 24 were girls and 6 were boys. The majority belonged to the Christian community. One third had a history of consanguinity or family history of similar illness. Sex assignment was appropriate in most. Karyotyping was done in half. Half the patients had adequate follow up and 17 OHP measurements. Only 7 out of 30 children had normal height for age. Bone age was done in 16 patients only. Most were on hydrocortisone. The average age of genital surgery was 31 months.

Hypothyroidism.

Hypothyroidism, due to deficiency of circulating thyroid hormones, is a disease with wide ranging symptoms and signs affecting many systems and presenting to various specialists. Once suspected it can be easily diagnosed by a simple blood test measuring serum thyroxine (T4) and thyroid stimulating hormone (TSH) levels. Treatment of hypothyroidism is by giving levothyroxine orally, and the dose is to be titrated to keep the serum TSH within the normal range. The clinical entity of subclinical hypothyroidism, characterised by normal T4 and elevated TSH is being diagnosed more frequently, and is emerging as a new indication for thyroxine therapy.