Association of vitamin B12 deficiency in people with type 2 diabetes on metformin and without metformin: a multicenter study, Karachi, Pakistan.

OBJECTIVE: To assess the prevalence of vitamin B12 deficiency in people with type 2 diabetes mellitus (T2DM) on metformin and without metformin. METHODOLOGY: Between May 2018 and January 2019, this prospective multicenter observational study recruited participants from seven centers in four provinces of Pakistan (Sindh, Punjab, Baluchistan and Khyber Pakhtunkhwa). Participants with T2DM treated with metformin for >2 years and those not on metformin underwent assessment of hemoglobin, vitamin B12, homocysteine and diabetic neuropathy (vibration perception threshold (VPT) >15V) and painful diabetic neuropathy (Douleur Neuropathique 4 (DN4) ≥4) and Diabetic Neuropathy Symptom (DNS) score ≥1. RESULTS: Of 932 subjects, 645 (69.2%) were treated with metformin, while 287 (30.8%) were not on metformin. Overall, B12 deficiency (<200 pg/mL) was significantly higher in metformin users of 25 (3.9%), compared with non-metformin users of 6 (2.1%), while B12 insufficiency (200-300 pg/mL) was significantly lower in metformin users of 117 (18.4%) compared with non-metformin users of 80 (27.9%). Subjects with B12 deficiency and insufficiency with hyperhomocysteinemia (≥15) were found in 19 (76%) µmol/L and 69 (60.5%) µmol/L in metformin users compared with 6 (100%) µmol/L and 57 (73.1%) µmol/L in non-metformin users, respectively. VPT>25 and DN4 score ≥4 were significantly higher in B12-deficient metformin users compared with non-metformin users. Similarly, DNS score ≥1 was non-significantly higher in B12-deficient metformin users compared with non-metformin users. CONCLUSION: This study shows that vitamin B12 insufficiency was frequently found in our population and may progress into B12 deficiency. It is also associated with neuropathy in subjects on metformin. Further interventional studies to assess the benefit of B12 treatment on painful neuropathy in patients on metformin may be warranted. B12 levels may be checked in people with T2DM using metformin for >2 years.

Comparison of ankle-brachial index (ABI) measured by an automated oscillometric apparatus with that by standard hand-held doppler in patients with Type-2 diabetes.

OBJECTIVE: To compare the difference between an automated oscillometric ABI measurement as compared to standard hand-held doppler ABI in patients with Type-2 diabetes. METHODS: This prospective study was conducted at foot clinic of Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University (BMU), a tertiary care unit, Karachi-Pakistan. The duration of study was February 2018 to March 2018. Patients with Type-2 diabetes attending the outpatient department (OPD) of foot clinic, irrespective of their symptoms were included. Baseline demographic, anthropometric measurements and biochemical parameters were recorded. The ABI was calculated with both devices by an automated oscillometric machine and standard hand-held doppler with the same investigator. RESULTS: Total of 93 patients with Type-2 diabetes, 18 (19.4%) females and 75(80.6%) males were recruited. Mean age was 54.67±9.59 years and mean systolic/diastolic blood pressure was 131.38±20.2/ 80.36±10.23mmHg. Most of the patients had poor glycemic control at presentation with a mean HbA1c of 9.56±2.44%. Mean standard handheld doppler ABI and automated oscillometric ABI was 1.28±1.08 and 1.07±0.23 for right foot (mean difference = 0.21; P= 0.075), and 1.14±0.45 and 1.1±0.25 for left foot (mean difference =0.04; P=0.434), respectively. Similarly, sensitivity and specificity between two modalities was observed 60% and 93.90% for right foot, meanwhile, 60% and 97.40% for left foot, respectively. CONCLUSION: An automated oscillometric method is comparable with standard handheld-doppler method. It is cost effective, convenient and less time consuming, can be widely used to measure ABI without special training.

Impact of multidisciplinary foot care team on outcome of diabetic foot ulcer in term of lower extremity amputation at a tertiary care unit in Karachi, Pakistan.

To compare the outcomes of diabetic foot ulcers (DFU) in terms of healing and lower extremity amputation (LEA) rate before and after training of multidisciplinary foot care team (MDFCT). Subjects were categorised into two groups; Group-A cases seen between 1997 and 2006 (before upgrading of training and services of MDFCT) and Group-B cases seen between 2007 and 2016 (after upgrading of training and services of MDFCT). Baseline demographic characteristics, biochemical results, and outcomes of DFU in terms of healing or amputation were analysed by using statistical package social science (SPSS) version 20. Total 7994 DFU cases seen, 888 in group A and 7106 in group B. Mean age of patients was 53.80 ± 10.40 years and mean haemoglobin (HbA1c) was 10.12 ± 2.44. Overall, decreasing trends of amputations were observed from baseline 27.5% to 3.92% during the period of 20 years. In group A, 479 (78.8%) subjects healed completely compared with 3806 (89.1%) in group B. Significant reduction in toe amputations ([13.81%] vs [8.11%]) and below knee amputations [(5.26%) vs (1.82%)] were seen. Similarly, rates of above knee amputation ([1.80%] vs [0.35%] P-value 0.008) in two groups was also significant. Significant improvement was observed in outcomes of DFU in terms of amputation through multidisciplinary team approach.

Protein requirement and its intake in subjects with diabetic foot ulcers at a tertiary care hospital.

OBJECTIVE: To assess the protein intake and requirement among subject with type 2 diabetes having foot ulcers. METHODS: This study was conducted at Baqai Institute of Diabetology & Endocrinology (BIDE), a tertiary care diabetes centre of Karachi, Pakistan among people with type 2 diabetic foot ulcer attending foot clinic from January 2012 to March 2015. The baseline characteristics, dietary intake and laboratory investigations of the study participants were obtained through electronic hospital database "Health Management System" (HMS) based on the 24 hours dietary recall interview. Total grams of protein were calculated from each food group consumed by the subject. Protein intake of the subjects was recorded in mean grams and the protein requirement was calculated according to their body weight. The comparison of intake and requirement of protein choices was done through comparing the mean of both variables. SPSS version 13 was used for analysing the results. RESULTS: A total of 542 subjects were included in the study, 365 (67.2%) were males and 178 (32.8%) were females. Mena age of the subject was 54.61±10.51 (yrs) with the duration of diabetes and mean body mass index were 14.22±7.98 (yrs) and 26.65±5.38 (kg/m2), respectively. The dietary records showed the protein intake of subjects with diabetic foot ulcer is not appropriate when compared to daily requirement. Mean grams of protein intake is 76.87gms in males and 56.84gms in females. On the other-hand protein requirement is much higher than the intake, which is 219.5gms in males and 130.2gms in females. CONCLUSION: Dietary counselling should be a part of the treatment among subjects with diabetic foot ulcer to identify their nutritional needs and suggesting them better option to fulfil their protein requirement essential for wound healing process.

Microbiological pattern of diabetic foot infections at a tertiary care center in a developing country.

OBJECTIVE: To determine the microbiological profile and antibiotic susceptibility patterns of organisms isolated from diabetic foot ulcers in a tertiary care hospital Karachi, Pakistan. METHODS: This descriptive study was conducted at the Baqai Institute of Diabetology and Endocrinology (BIDE), from January 2013 to March 2014. Bone, pus and tissue samples were collected from 342 patients with diabetic foot infections and inoculated on appropriate media. Antibiotic susceptibility tests were done by Kirby Bauer disk diffusion method. RESULTS: A total of 671 aerobic bacteria were isolated from 473 specimens with an average of 1.45 isolates per specimen. Poly-microbial infection was 56.87%. Gram- negative isolates were predominant 76.27%.Staphylococcus aureus was most frequent among Gram-positive 20.7% and Escherichia coli 15.72% in Gram negative isolates. MRSA was found in 26.76% Staphylococcus aureus. About 33.48% of antimicrobial resistant isolates were observed. CONCLUSIONS: In our study, Gram negative aerobes were predominant in the diabetic foot infections. A significant number of MDR isolates were also observed in this cohort. Delayed referral and inappropriate use of broad spectrum antibiotics may be the main cause of increase in the frequency of MDR isolates.

Characteristics of a large cohort of patients with diabetes having at-risk feet and outcomes in patients with foot ulceration referred to a tertiary care diabetes unit.

To identify in a large population cohort the clinical and biochemical characteristics of patients with diabetes at risk of foot ulceration and outcomes in those with foot ulcers. All patients with diabetes attending Baqai Institute of Diabetology and Endocrinology from January 2004 to April 2012 included in the study. Clinical, biochemical and socio-demographic data were collected and patients were categorised into those at no risk of ulceration, at risk of ulceration and those with foot ulcer, according to the University of Texas classification. Patients with foot ulceration followed for their final outcome, that is complete healing, persisted non-healed ulcer, lower extremity amputation, lost to follow-up or death. A total of 18 119 patients with diabetes underwent assessment, 3576 (19·7%) patients defined as at high risk for foot ulceration and 3731 (20·6%) presented with foot ulcer. Age, male gender, hypertension, higher glycated haemoglobin (HbA1c), history of smoking and presence of neuropathy were risk factors (P < 0·000) for foot ulceration. Amputation rate in patients with foot ulceration was significantly related to severity of ulceration at presentation. Preventive foot care practices were followed by 19·02% patients. One thousand eight hundred seventy three (50·2%) patients completely healed, 293 (11%) patients underwent amputation and 397 (10·1%) patients continued to be treated in the foot clinic. All patients with diabetes should be screened for neuropathy to identify those at risk of foot ulceration, as it is the major contributory factor for foot ulceration. The final outcome of foot ulceration was determined by the severity and grade of ulcer at presentation.

Use of locally made off-loading techniques for diabetic plantar foot ulcer in Karachi, Pakistan.

The aim of this study was to evaluate the effectiveness of applying locally made pressure off-loading techniques on plantar foot ulcer in individuals with diabetes. This prospective study of 70 diabetic patients was conducted at the foot clinic of Baqai Institute of Diabetology & Endocrinology. Plantar foot ulcer, stages 1A and 2A according to the University of Texas classification, was treated by using three off-loading techniques: modified foot wear (sandal), modified plaster of Paris cast with plywood platform and Scotchcast boot. The outcome was assessed at either complete wound healing (defined as complete epithelialisation) or at 12 weeks, whichever came first. Of the 70 patients, 24 were in modified foot wear group, 23 in modified plaster of Paris cast and 23 in Scotchcast boot group. There was almost equal proportion of patients healed within 12 weeks period treated with these three off-loading techniques, i.e. 22 (95·7%) for modified foot wear group, 19 (95%) for modified plaster cast and 18 (94·7%) for Scotchcast boot group. No significant difference was observed in median healing time and cumulative wound survival at 12 weeks in the three off-loading techniques. Modified foot wear group was the most cost effective ($7) amongst the three off-loading techniques. It is concluded that in this cohort, no significant difference in healing time was observed in the three off-loading techniques, although modified foot wear (sandal) was found to be a more cost-effective treatment modality.

A multinational, observational study to investigate the efficacy, safety and tolerability of acarbose as add-on or monotherapy in a range of patients: the Gluco VIP study.

BACKGROUND AND OBJECTIVES: The burden of type 2 diabetes mellitus is growing rapidly, particularly in the Asia-Pacific region. The aim of this international, large-scale, observational study was to investigate the efficacy and tolerability of the antidiabetic agent acarbose as add-on or monotherapy in a range of patients with type 2 diabetes, including those with cardiovascular morbidities. The majority of practices were included from high-burden regions (predominantly those in the Asia-Pacific region). METHODS: This was an observational study conducted in 15 countries/regions. Adults with pre-treated or untreated type 2 diabetes prescribed acarbose as add-on or monotherapy were eligible. Two-hour postprandial blood glucose (2-h PPG), glycosylated haemoglobin (HbA1c) and fasting blood glucose (FBG) were measured over a 3-month observation period. RESULTS: A total of 15,034 patients were valid for the efficacy analysis and 15,661 for the safety analysis (mean age was 57.6 years and 92.6 % of patients were Asian). Mean (SD) 2-h PPG decreased by -71.9 (62.3) mg/dL, to 170.2 (46.5) mg/dL at final visit (after 12.8 [4.1] weeks). Mean HbA1c decreased by -1.1 % (1.3) to 7.2 % (1.1) and mean FBG decreased by -33.0 (43.3) mg/dL to 124.8 (30.5) mg/dL. Acarbose was effective regardless of the presence of cardiovascular co-morbidities or diabetic complications. The efficacy of acarbose was rated 'very good' or 'good' in 85.5 % of patients, and tolerability as 'very good' or 'good' in 84.9 % of patients. Drug-related adverse events, mainly gastrointestinal, were reported in 490/15,661 patients (3.13 %). CONCLUSION: The results of this observational study support the notion that acarbose is effective, safe and well tolerated in a large cohort of Asian patients with type 2 diabetes.

Switch from biphasic human insulin 30 to biphasic insulin aspart 30 in Pakistani subjects.

OBJECTIVE: To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes subjects switched from biphasic human insulin 30 (BHI 30) in the Pakistani subgroup of the multinational, prospective, non-interventional A1chieve study. METHODS: Subjects who switched therapy from BHI 30 to BIAsp 30 were included in this analysis. Serious adverse drug reactions (SADRs, including major hypoglycaemia) and effectiveness parameters (glycated haemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPPG], systolic blood pressure [SBP]) and body weight were evaluated at the end of 24 weeks. RESULTS: A total of 152 subjects (79 males, 73 females; mean age, 53.4 +/- 10.3 years; BMI, 28.4 +/- 5.8 kg/m2) with an average diabetes duration of 11.2 +/- 4.8 years switched therapy from BHI 30 to BIAsp 30. The mean pre-study BHI 30 dose was 0.66 +/- 0.25 IU/kg and the mean starting BIAsp 30 dose was 0.65 +/- 0.23 U/kg, titrated up to 0.77 +/- 0.22 U/kg after 24 weeks. No SADRs were reported. From baseline to Week 24, overall hypoglycaemia did not change and no major hypoglycaemia was reported at Week 24. HbA1c levels decreased significantly from 9.1 +/- 1.1% at baseline to 7.4 +/- 0.7% (57 +/- 8 mmol/mol) at Week 24 (p < 0.001). Significant improvements in FPG, post-breakfast PPPG and SBP were reported (p < 0.001). CONCLUSION: Switching from BHI 30 to BIAsp 30 was well tolerated and improved glucose control without an increased incidence of hypoglycaemia in this Pakistani cohort.

Safety and effectiveness of biphasic insulin aspart 30 (Biasp 30) in people with type 2 diabetes mellitus in the pakistani population: results from the A1chieve study.

OBJECTIVE: To explore the safety and effectiveness of treatment with the insulin analogue, biphasic insulin aspart 30 (BIAsp 30), in people with type 2 diabetes mellitus (T2DM) in a subgroup of a Pakistani population from the A1chieve study. METHODS: A1chieve was a 24-week, international, prospective, multicentre, open label, observational, non-interventional study designed to evaluate the safety and clinical effectiveness of 66,726 people with T2DM who were initiated with basal insulin detemir, fast actinginsulin aspart, and BIAsp 30 (30% soluble insulin aspart, 70% protamine-crystallized insulin aspart). The study was conducted in 28 countries across Asia, Africa, Latin America, and Europe. Here, we report data from a subgroup of 762 people with T2DM from the Pakistani cohort (insulin naïve and insulin users) who were treated withpremix insulin (BIAsp 30) +/- oral antidiabetic drugs (OADs). RESULTS: The decrease in HbAlc at week 24 was statistically significant in the entire cohort, the insulin naïve, and insulin users (1.7 +/- 1.1%, 1.8 +/- 1.3% and 1.7 +/- 0.9%, respectively, p<0.001 for all).There was a statistically significant decrease in the mean fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) from baseline toweek 24 in the entire cohort, in the insulin naïve and in the insulin users with BIAsp 30 treatment (p<0.001 for all).No major hypoglycaemic events were reported during the entire study period. There was a statistically significant decrease in the systolic blood pressure (SBP) in all groups (p<0.001). The improvement in the quality of life score (QoL)was statistically significant in all groups (p<0.001 for all). CONCLUSION: BIAsp 30 treatment appeared to be well tolerated and effective as indicated byimproved glycaemiccontrol and QoL in people with T2DM in the Pakistani population after 24 weeks.

Trends of type 1 diabetes in Karachi, Pakistan.

OBJECTIVE: Our study aims to assess the presentation, prevalence, and associations of acute and chronic complications in subjects with type 1 diabetes mellitus (T1DM) at their first visit to outpatient departments. STUDY DESIGN AND SETTING: Study was carried out at two centers, Diabetic Association of Pakistan and WHO Collaborating Centre and Baqai Institute of Diabetology and Endocrinology, Karachi. Records of 591 T1DM subjects divided into two groups were studied. Group 1 (62.1%, n = 367) includes patients with known T1DM and group 2 (n = 224, 37.9%), newly diagnosed T1DM. Clinical features [polyuria, polydipsia, polyphagia, history of weight loss, and history of diabetic ketoacidosis (DKA)] were recorded. Biochemical parameters including fasting plasma glucose, 2-h postprandial plasma glucose, hemoglobin A1c, urinary ketones, and proteinuria were recorded. Arterial blood gases was done in suspected cases of DKA. RESULTS: In group 1, male predominance was seen (57.8 vs. 42.2%). Mean age at presentation was 19.1 +/- 10 yr. Mean duration of diabetes was 16 +/- 9 yr. Two percent subjects presented with DKA, while 21% had a history of DKA. Among the subjects with >10 yr of diabetes, 20.1% had hypertension, 5.5% had nephropathy, 2.9% had neuropathy, and 7.7% had retinopathy. In group 2, 224 T1DM subjects were identified, with mean age of 17 +/- 11 yr. Equal number of males (50.9%) and females (49.1%) were diagnosed at their first presentation. Most subjects (40.8%, n = 91) diagnosed between 11 and 20 yr of age presented with polyuria (81.3%), polydipsia (77.2%), polyphagia (56.7%), and weight loss (79.5%). Ketonuria was positive in 4.9%, while 5.8% presented with DKA. CONCLUSIONS: This is the first study in Pakistan to assess the mode of presentation and prevalence of acute and chronic complications in T1DM. Larger scale prospective studies are needed to have more detailed informative data.

Role of wound classification in predicting the outcome of diabetic foot ulcer.

OBJECTIVE: To compare the effectiveness of Wagner and University of Texas (UT) classification systems of diabetic foot ulcers in directing appropriate therapy and possibly predicting outcomes. METHODS: A total of 383 patients with foot ulcer were seen. Details of socio-demographic and clinical profiles of 200 patients were completely available. Patients were assessed and classified into different grades and stages according to Wagner's and UT classification systems. Their duration of healing was recorded. The outcome endpoints were defined as complete healing, major or minor amputations, or expired. RESULTS: Out of the 200 subjects, 65% were males and 35% were females. Mean age in males was 53.04 +/- 10.33 years and in females was 51.14 +/- 9.94 years. Average duration of treatment in males was 109.68 +/- 82.26 days and in females was 85.10 +/- 61.97 days. Forty five percent of the subjects had neuropathic ulcers. Median healing time increased with increase in Wagner grade and UT grade and stage. The higher the UT grade and stage at the time of presentation, the less the chances of ulcer to heal within the study period. CONCLUSION: Our study has shown that grading and staging of diabetic foot ulcer affects and predicts the outcome. Amputation rates increase with increase in grade. Addition of stage to grade in UT classification helps further on assessing the severity of wound at the time of presentation and shows better association with the outcome.

Comparison of risk factors for diabetes in children of different socioeconomic status.

OBJECTIVE: To compare the risk factors for diabetes in children of two different socioeconomic status. DESIGN: A cross-sectional analytical study. PLACE AND DURATION OF STUDY: Visits to one government (low income) and two private (middle income) schools of Karachi in 1999 and 2000. PATIENTS AND METHODS: A total of 260 children; 157 children (mean age 12.10 +/- 4 years) from low-income group and 103 children (mean age 10.6 +/- 0.9 years) from middle-income group were surveyed. Data of physical fitness score (PFS) and BMI was calculated. Dietary records were taken by 24 hours self-reported diet recall charts of two weekdays. Knowledge about health was obtained by a questionnaire given to children and mothers. RESULTS: A significant difference was found in the mean age of low-income and middle-income groups (p-value < 0.001). Significant association was seen in low-income group compared to middle-income group on the basis of TV viewing (p-value = 0.04). BMI (p-value = 0.011) and positive family history of diabetes (p-value < 0.001). Forty-seven percent (n=74) of children from low-income group while 51% (n=53) of middle-income group had poor knowledge about health. The children in both the groups also consumed inadequate amount of calories, the diet being poor in fruit, vegetables and milk and high in the fat content. CONCLUSION: Although children in both the groups had increased risk factors for diabetes the difference between the two socioeconomic groups was significant in terms of middle-income children having more risk. Thus, changes in lifestyle and behaviour including diet is needed in this high risk group to prevent future generations from developing diabetes.