Change in pulmonary function tests and their relation to the serum levels of ceruloplasmin, copper and superoxide dismutase in patients suffering from Type-1 and Type-2 diabetes.

Objective: To correlate the serum levels of ceruloplasmin (Cp), copper (Cu), and superoxide dismutase (SOD) with pulmonary function tests (PFTs) in non-diabetics (controls) and patients suffering from Type-1 and Type- 2 diabetes. Methods: The comparative cross-sectional study of 348 participants was performed at the Baqai Institute of Diabetes and Endocrinology (BIDE) - Karachi, Pakistan, from February 2019 to September 2020. Individuals having diabetes-related complications, asthma, chronic obstructive pulmonary disease, chest infection, pregnant women and smokers were excluded. A total of 348 participants were included into three groups after signing informed consent. The control group had 107 non-diabetic participants, with an age range of 6 to 60 years. The diagnosed T1D group (n=107) had an age range of 6 to 25 years. While diagnosed T2D group (n=134) had an age range of 26 to 60 years. During the fasting state, anthropometric parameters, blood pressure, spirometry, and a venous blood sample (5ml) were collected to measure serum Cp, serum Cu, serum SOD, and HbA1c levels by using commercially available kits. The SPSS, version 21, was used for data analysis. Results: The reduced FVC (p-value <0.001), FEV1 (p-value <0.001), and PEFR (p-value <0.001) were found in both groups of diabetes. However, the lower levels of serum Cu (p-value <0.001), SOD (p-value <0.001), and significantly increased values of FEV1/ FVC (p-value <0.001) and Cp levels (p-value 0.030) were found only in T2D group as compared to T1D and controls. The study found no significant correlation of PFTs and serum Cp, Cu, and SOD levels in patients suffering from T1D and T2D. Conclusion: Hyperglycemia leads to more non-enzymatic glycosylation of tissue proteins that reflects reduced PFTs and increased Cp; particularly in T2D, which may alter lung tissue's physiology. Moreover, the study showed no correlation of PFTs with the Cp, Cu, and SOD in patients suffering from T1D and T2D.

Association of Hepcidin levels in Type 2 Diabetes Mellitus treated with metformin or combined anti-diabetic agents in Pakistani population.

Objective: To evaluate the impact of hepcidin and ferritin in pathogenesis and prognosis of type 2 diabetes mellitus subjects taking only metformin or combined anti-glycaemic agents. METHODS: The observational case-control study was conducted at the Department of Physiology, Baqai Medical University, Karachi, from August 2019 to October 2020, and comprised subjects from both genders who categorised into equal groups as non-diabetic controls, newly-diagnosed type 2 diabetes mellitus patients without any treatment, type 2 diabetes mellitus patients with exposure to metformin only, type 2 diabetes mellitus patients taking oral hypoglycaemic agents along with metformin, type 2 diabetes mellitus patients taking only insulin, and type 2 diabetes mellitus patients taking insulin and oral hypoglycaemic agents. Fasting plasma glucose was determined using glucose oxidase-peroxidase method, glycated haemoglobin by high performance liquid chromatography, high-density lipoprotein and low-density lipoprotein by direct methods, cholesterol by cholesterol oxidase phenol 4-amino antipyrine peroxidase and triglycerides by glycerol phosphate oxidase-phenol 4-amino antipyrine peroxidase method. Serum levels of ferritin, insulin and hepcidin were evaluated using Enzyme-linked immunosorbent assay. Insulin resistance was assessed using homeostasis model assessment for insulin resistance. Data was analysed using SPSS 21. RESULTS: Of the 300 subjects, there were 50(16.66%) in each of the 6 groups. Overall, there were 144(48%) males and 155(51.66%) females. The mean age was significantly lower in the control group 34.72±7.87 compared to all the diabetic groups (p<0.05), and the same was the case with respect to all the parameters (p<0.05) except high-density lipoprotein (p>0.05). Besides, hepcidin level was significantly higher in the control group (p<0.05). Ferritin levels were significantly increased in newly-diagnosed T2DM subjects compared to the controls (p<0.05) while all other groups showed decreased ferritin levels (p<0.05). Hepcidin gave inverse correlation with glycated haemoglobin only in diabetics taking only metformin (r = -0.27, p=0.05). CONCLUSIONS: Anti-diabetes drugs not only addressed type 2 diabetes mellitus, but also reduced levels of ferritin and hepcidin that are found to play a role in diabetes development.

Effects of varying levels of gonadotropins and estrogen in adolescent females having type 1 diabetes with their impact on health-related quality of life in Karachi Pakistan.

The purpose of this study is to evaluate quality of life, the gonadotropins and estrogen levels in type 1 diabetic adolescent females. This cross-sectional study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE). The Diabetes quality of life for youth questionnaire (DQOLY) was used to evaluate quality of life. FSH was found to be significantly lower in Type 1 Diabetes. HbA1c had a significant inverse moderate correlation with FSH(-0.300*).In Type 1 Diabetes, FSH had a positive moderate correlation with LH(0.415*), (P-value<0.05). LH and estradiol levels were almost similar in both groups. Overall mean percentage score of DQOLY questionnaire for Type 1 Diabetes was 26.94±1.36. Low QOL score was observed on the basis of impact on activities. Adolescent females with Type 1 Diabetes were found to be shorter and underweight than non-diabetic adolescent females. Lower height and weight of the diabetes as compared to controls cannot be attributed to only metabolic control, suggesting other mechanisms for short stature. Control on metabolism has always been the target for diabetes treatment for ensuring the improved prognosis of disease but also for the quality of life in Type 1 diabetes.

Glycemic status and general characteristics among individuals with undiagnosed diabetes; findings from second National Diabetes Survey of Pakistan 2016-2017 (NDSP 08).

BACKGROUND AND AIM: To observe the glycemic status among individuals with undiagnosed diabetes in urban and rural areas of all four provinces of Pakistan. METHODS: The findings of this study are obtained from the second National Diabetes Survey of Pakistan (NDSP) 2016-2017, a nationwide epidemiological survey. Out of 12,486 individuals approached, 10,834 participants agreed to be included in the second NDSP. An oral glucose tolerance test was used to assess undiagnosed diabetes individuals according to World Health Organization criteria. RESULTS: The overall weighted prevalence of undiagnosed diabetes was 7.1% (2.4% in urban and 4.7% in rural areas). Based on isolated fasting plasma glucose or 2-h post 75 gm glucose load or combining both, the weighted prevalence of undiagnosed diabetes was 43.5%, 17.6%, and 38.9%, respectively. Out of the 43.5% of individuals, 15.3% had fasting plasma glucose higher than 250 mg/dl at the time of presentation. Among all the individuals, 23.7% were found to be of less than 40 years of age, 29.2% had a positive family history of diabetes, 80.8% were abdominal obese, 53.8% were hypertensive, and 98% were dyslipidemic. In comparison to the elder group, poor glycemic control of ≥10% HbA1c was observed in most of the younger age groups (p < 0.05). CONCLUSION: A significant number of people remain undiagnosed in this part of the world. The glycemic status along with the other associated risk factors at the time of presentation is alarming. Thus, for the early detection of diabetes, awareness and education in the community are crucial. Hence, long-term complications of diabetes can be prevented.

Association of fibrinogen and plasminogen activator inhibitor-1 with diabetes mellitus.

As the state of hyperfibrinogenemia in diabetes patients occurs due to hyperglycemia which also activates the coagulative cascade ultimately stimulating hepatic fibrinogen synthesis and thus increases clotting factors and PAI-1 levels in the blood. Therefore, in present study our aim is to correlate between type of diabetes and plasma fibrinogen level and plasminogen activator inhibitor-1. This cross sectional study was conducted at Baqai Medical University (BMU) with the collaboration of Baqai Institute of Diabetology and Endocrinology, Karachi. Data was collected from 161 subjects, out of which 51 were control and 55 were subjects in each type 1 diabetes, type 2 diabetes simultaneously. Anthropometric measurements included measurement of weight, height, BMI and blood pressure which were done for each participant. Blood sugar levels and glycated hemoglobin, lipid profile, PAI-1 and fibrinogen were measured in cases and controls. Out of 161 subjects, 80 (49.7%) were male and 81 (50.3%) were female with mean age of 37.75±1.25 years. Fibrinogen level was significantly decreased in healthy subjects as compared to type 1 and type 2 diabetes subjects P-value<0.0001, however no significant difference was observed in fibrinogen level of type 1 diabetes subjects and type 2 diabetes subjects. Plasminogen activator inhibitor-1 of type 2 diabetes subjects was significantly increased as compared to type 1 diabetes subjects (P-value<0.05) but not significantly different to healthy subjects (P-value>0.05). Since, fibrinogen and plasminogen activator inhibitor type 1 was increased in diabetes patients this predisposed them to increased risk of coronary artery disease, our study further supports the clinical observation that diabetes is a thrombophillic condition.

Glycated hemoglobin (HbA1c) as diagnostic criteria for diabetes: the optimal cut-off points values for the Pakistani population; a study from second National Diabetes Survey of Pakistan (NDSP) 2016-2017.

AIM: Glycated hemoglobin (HbA1c) cut-off values as diagnostic tool in diabetes and prediabetes with its concordance to oral glucose tolerance test (OGTT) in Pakistani population. METHODOLOGY: Data for this substudy was obtained from second National Diabetes Survey of Pakistan (NDSP) 2016-2017. With this survey, 10 834 individuals were recruited and after excluding known subjects with diabetes, 6836 participants fulfilled inclusion criteria for this study. Demographic, anthropometric and biochemical parameters were obtained. OGTT was used as standard diagnostic tool to screen population and HbA1c for optimal cut-off values. Participants were categorized into normal glucose tolerance (NGT), newly diagnosed diabetes (NDD) and prediabetes. RESULTS: Out of 6836 participants, 4690 (68.6%) had NGT, 1333 (19.5%) had prediabetes and 813 (11.9%) had NDD by OGTT criteria with median (IQR) age of 40 (31-50) years. Optimal HbA1c cut-off point for identification of diabetes and prediabetes was observed as 5.7% ((AUC (95% CI)=0.776 (0.757 to 0.795), p<0.0001)) and 5.1% ((AUC (95% CI)=0.607 (0.590 to 0.624), p<0.0001)), respectively. However, out of 68.6% NGT subjects identified through OGTT, 24.1% and 9.3% participants were found to have prediabetes and NDD, respectively by using HbA1c criteria. By using both OGTT and HbA1c criteria, only 7.9% and 7.3% were observed as prediabetes and diabetes, respectively. CONCLUSION: Findings from second NDSP demonstrated disagreement between findings of OGTT and HbA1c as diagnostic tool for Pakistani population. As compared with international guidelines, HbA1c threshold for prediabetes and NDD were lower in this part of world. HbA1c as diagnostic tool might require ethnic or regional-based modification in cut-off points, validated by relevant community-based epidemiological surveys.

Glucagon-like peptide 1 and its association with dipeptidyl peptidase IV in subjects with various degrees of glucose tolerance.

Dipeptidyl peptidase IV (DPP-4) and Glucagon like peptide 1 (GLP-1) has profound effect on insulin and glucagon secretion; ultimately decreasing glucose levels. We find out the association of GLP-1 levels and DPP-4 in normal, impaired and newly diagnose type 2 diabetic glucose tolerance. Prospective case control study was conducted at Department of Physiology, Baqai Medical University by the collaboration of Baqai Institute of Diabetology and Endocrinology; Karachi-Pakistan. Study groups were categorized into three groups Control, Impaired glucose tolerant (IGT) and newly diagnose type 2 diabetes mellitus (NDD). Biochemical parameters were estimated by international standard protocols. Logistic regression analysis and Chi square test with statistical significance at p value <0.05 were applied. DPP-4 concentrations were significantly lower in NDD participants compared to control and IGT participants (p=0.01), whereas GLP-1 levels were significantly higher in Control than Impaired glucose tolerant and NDD (p = 0.013). GLP1 levels and SBP were also found to be positively correlated with serum DPP4 levels in NDD group (p<0.05). GLP1 and DPP4 levels in NDD group (p<0.05) and in controls (p<0.001) respectively showed strong significant positive correlation. Effective correlation between GLP1 and DPP4 was found as both contribute to control hyperglycemia in NDD and impaired glucose tolerant people.

Neutrophil-to-lymphocyte ratio and microvascular complications in subjects with type 2 diabetes: Pakistan's perspective

Background/aim: The aim of this study is to find the association between diabetic microvascular complications and the neutrophil-to-lymphocyte ratio (NLR) in subjects with type 2 diabetes. Materials and methods: This was a retrospective study based on hospital data records from January 2005 to May 2016 at the Baqai Institute of Diabetology and Endocrinology. The eligibility criteria included subjects with type 2 diabetes with their latest complete blood count while subjects with conditions such as chronic inflammation, cancer, heart failure, and end-stage renal disease were not eligible for inclusion. Subjects were divided into two groups: one with any microvascular complications and the other with no microvascular complications. Body mass index, anthropometric measurements, and blood pressure were measured. Results: Out of 5620 type 2 diabetic subjects, 3202 (57%) were male and (2418) 43% were female. Among these, 3374 diabetic subjects had one or more microvascular complications and 2246 had no microvascular complications. The NLR was found to be 1.14 times higher in diabetic subjects with at least one microvascular complication as compared to diabetic subjects without any complications (4.34 ± 3.32 vs. 3.36 ± 2.67; P < 0.0001). Factors likely associated with microvascular complications were high levels of NLR, HbA1c, serum creatinine, and systolic blood pressure and longer duration of diabetes. Conclusion: According to the results, the NLR is an efficient, cheaper, and readily available marker of inflammation and it is known as an important predictor for the existence of microvascular complications in subjects with type 2 diabetes.

Framingham risk score in impaired glucose tolerant population: A sub analysis of Diabetes Prevention and Awareness Program of Pakistan.

OBJECTIVE: To assess the 10-year risk of coronary artery disease (CAD) in subjects with impaired glucose tolerance (IGT) using Framingham risk score. METHODS: Data for this study was collected from Diabetes Prevention and Awareness Program. Primary prevention team visited different primary health care centers, factories, service organizations and offices within Karachi, Pakistan. IGT was diagnosed according to World Health Organization criteria after taking informed consent. Information regarding social-demography, dietary habits and physical activities were obtained by a designed questionnaire on one-to-one based interview. Framingham risk score (FRS) was used to assess risk of developing CAD. RESULTS: A total of 315 subjects with IGT were recruited for the study. Mean age of subjects was 44.1 ± 9.8 years and mean BMI was 27.3 ± 5.0 kg/m2. Overall, 31.4% of the participants were at risk of having CAD. Males were 6.4 times and hypertensive subjects were 2.44 times more likely to have CAD in next 10 years. CONCLUSION: According to the findings of the study, male and hypertensive IGT subjects were more likely to develop CAD in next 10 years. Community based awareness programs are needed to educate people regarding healthy lifestyle in order to reduce the risk of IGT and CAD.

Common variant within the FTO gene, rs9939609, obesity and type 2 diabetes in population of Karachi, Pakistan.

AIM: To determine the effect of genetic variants within the FTO gene (rs9939609) on obesity related traits and type 2 diabetes in South Asian population of Karachi, Pakistan. METHODS: A case-control study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University situated in Karachi. A total of 296 patients with known type 2 diabetes and 198 controls aged greater than and equal to 45 years were recruited. The Anthropometric, clinical and biochemical data was collected on a structured questionnaire. Single nucleotide polymorphism (SNP) in FTO gene was identified by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Association between the single nucleotide polymorphism and categorical variables such as type 2 diabetes and obesity category was tested through logistic regression analysis. RESULTS: We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes. Significant difference was observed in frequency of FTO genotype when diabetic subjects were compared with controls in co dominant, dominant and recessive models. This association remained significant even after adjusting for body mass index (BMI) and for waist circumference. The frequency of homozygous risk Alleles (AA) was found to be higher in obese & overweight (≥ 23 kg/m(2)) and females with central obesity in our study population. The association of FTO variant with BMI and central obesity does not reach to statistical significance. CONCLUSION: In the study population of South Asian ancestry, variants of the FTO gene predispose to type 2 diabetes, but not entirely through their effect on BMI.

Differences in various biochemical and clinical parameters with respect to family history of Non Communicable Diseases in fourth year MBBS students of Karachi, Pakistan.

OBJECTIVE: To observe the differences of various biochemical and clinical parameters with respect to Family History (FH) of Non-communicable Diseases (NCDs) in fourth year Bachelor of Medicine, Bachelor of Surgery (MBBS) students. METHODS: This observational study was conducted at Baqai Institute of Diabetology & Endocrinology from December 2013 to January 2014. Total 50 medical students from Dow University of Health Sciences (DUHS) participated in the study. Statistical Package for Social Sciences (SPSS) version 13 was used to analyze the data. For cross tabulation and mean comparison z-test and t test were applied. RESULTS: Out of 50 subjects, there were 26 (52%) females. Mean age of the study population was 21.56 ± 0.90 years. Mean serum cholesterol levels with positive FH of NCDs was significantly higher than negative FH of NCDs (p=0.005). Mean value of low density lipoprotein (LDL) of positive family history of NCDs was found higher than those with negative FH (p=0.006) being statistically significant. The insulin levels in subjects with positive FH of NCDs were higher than subjects with negative FH of NCDs (p=0.685). However, serum leptin and plasma renin showed no significant difference with the negative FH of NCDs being higher compared to positive FH of NCDs (p=0.068) and (p=0.884) respectively. However, Waist circumference, Body mass index and central obesity in subjects with positive FH of NCDs shows increasing trend but no statistically significant difference (p > 0.05) was observed. CONCLUSION: In our study of various biochemical and clinical parameters with respect to FH of NCDs, Serum Cholesterol and LDL levels were observed higher and statistically significant.

Association of SNP rs9939609 in FTO gene with metabolic syndrome in type 2 diabetic subjects, rectruited from a tertiary care unit of Karachi, Pakistan.

OBJECTIVE: To determine the association of SNP in FTO gene, rs9939609, with Metabolic Syndrome (MS) in type 2 diabetic subjects at a tertiary care unit of Karachi, Pakistan. METHODS: We genotyped FTO rs9939609 SNP in 296 patients with type 2 diabetes from the Out Patient Department (OPD) of Baqai Institute of Diabetology and Endocrinology (BIDE). MS was defined on the basis of International Diabetes Federation (IDF) and National Cholesterol Education program (NCEP) criterion. Association between the rs9939609 SNP and MS was tested through chi-square and Z-tests by using odds ratio (OR) with 95% confidence intervals. RESULTS: The frequency of MS as defined by IDF criterion was significantly higher in female subjects as compared to male subjects (p= 0.006). Carriers of ≥ 1 copy of the rs9939609 A allele were significantly more likely to had MS (69.6%) than non-carriers (30.4%), corresponding to a carrier odds ratio (OR) of 0.52 (95% confidence interval [CI] (0.29-0.93), with a similar trend for the ATP III-defined MS."A" allele carriers under dominant model, carry all the criterion of MS more significantly as compared to non-carriers. CONCLUSION: The FTO rs9939609 SNP was associated with an increased risk for Metabolic Syndrome in type 2 diabetic populations at a tertiary care unit of Karachi, Pakistan.