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1.
Horm Res Paediatr ; : 1-9, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38986456

ABSTRACT

INTRODUCTION: Thyroid dyshormonogenesis (TDH) is a subgroup of congenital hypothyroidism with recessive inheritance resulting from disease-causing variants in thyroid hormone biosynthesis pathway genes, like DUOX2, TG, TPO, SLC5A5, SLC26A4, IYD, DUOXA2, and SLC26A7. Thyroid peroxidase (TPO) is a crucial enzyme involved in thyroid hormone biosynthesis and is one of the frequently mutated genes in patients with TDH. The purpose of the study was to describe the in silico and functional characterization of novel variants in TPO gene identified in patients with TDH. METHODS: We performed exome sequencing in Indian patients with TDH. In the current study, we describe the results of patients with TPO gene mutations. Exome sequencing results were further analysed by Sanger sequencing, computational studies, and in vitro functional studies such as immunofluorescence and enzyme assay. RESULTS: We identified nine biallelic disease-causing variants in the TPO gene in 12 patients from nine unrelated Indian families. Eight of the nine variants were novel. No recurrent variants were identified. Computational analysis of six missense variants showed that these amino acid substitutions caused changes in non-covalent interactions with the adjacent residues that may affect the TPO protein structure and function. In vitro experimental data using immunofluorescence assay showed that these variants did not affect the plasma membrane localization of the TPO protein but caused a significant loss of TPO enzymatic activity compared to the wild type. CONCLUSION: Our study revealed multiple novel pathogenic variants in TPO gene in Indian patients, thereby expanding the genotype spectrum. Functional studies helped us to reveal the pathogenicity of the missense variants.

2.
J Diabetes Sci Technol ; 15(1): 134-140, 2021 01.
Article in English | MEDLINE | ID: mdl-31282179

ABSTRACT

BACKGROUND: To compare glycemic variability (GV) indices between patients with fibrocalculous pancreatic diabetes (FCPD) and type 2 diabetes mellitus (T2D) using continuous glucose monitoring (CGM). METHODS: We measured GV indices using CGM (iPro™2 Professional CGM, Medtronic, USA) data in 61 patients each with FCPD and T2D who were matched for glycated hemoglobin A1c (HbA1c) and duration of diabetes. GlyCulator2 software was used to estimate the CGM-derived measures of GV (SD, mean amplitude of glycemic excursion [MAGE], continuous overall net glycemic action [CONGA], absolute means of daily differences [MODD], M value, and coefficient of variance [%CV]), hypoglycemia (time spent below 70 mg/dL, AUC below 70 mg/dL, glycemic risk assessment diabetes equation hypoglycemia, Low Blood Glucose Index), and hyperglycemia (time spent above 180 mg/dL at night [TSA > 180], AUC above 180 mg/dL [AUC > 180], glycemic risk assessment diabetes equation hyperglycemia, High Blood Glucose Index [HBGI], and J index). The correlation of GV indices with HbA1c, duration of diabetes, and demographic and biochemical parameters were also assessed. RESULTS: All the CGM-derived measures of GV (SD, MAGE, CONGA, MODD, and %CV), except M value, were significantly higher in the FCPD group than in the T2D group (P < 0.05). Measures of hyperglycemia (TSA >180, AUC >180, HBGI, and J index) were significantly higher in the FCPD group than in the T2D group (P < 0.05). The measures of hypoglycemia were not significantly different between the two groups. All the hyperglycemia indices showed a positive correlation with HbA1c in both groups. CONCLUSIONS: FCPD is associated with higher GV than is T2D. The findings of higher postprandial glycemic excursions in patients with FCPD could have potential therapeutic implications.


Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemia , Blood Glucose , Blood Glucose Self-Monitoring , Glycated Hemoglobin/analysis , Humans
3.
J Diabetes Sci Technol ; 15(6): 1313-1319, 2021 11.
Article in English | MEDLINE | ID: mdl-33322930

ABSTRACT

BACKGROUND: Detailed evaluations of hypoglycemia and associated indices based on continuous glucose monitoring (CGM) are limited in patients with diabetes of the exocrine pancreas. Our study sought to evaluate the frequency and pattern of hypoglycemic events and to investigate hypoglycemia-specific indices in this population. METHODS: This was a cross-sectional study comprising 83 participants with diabetes of the exocrine pancreas. CGM and self-monitoring of blood glucose (SMBG) were performed on all participants for a minimum period of 72 hours. The frequency and pattern of hypoglycemic events, as well as hypoglycemia-related indices, were evaluated. RESULTS: Hypoglycemia was detected in 90.4% of patients using CGM and 38.5% of patients using SMBG. Nocturnal hypoglycemic events were more frequent (1.9 episodes/patient) and prolonged (142 minutes) compared with day-time events (1.1 episodes/patient; 82.8 minutes, P < 0.05). The mean low blood glucose index was 2.1, and glycemic risk assessment diabetes equation hypoglycemia was 9.1%. The mean time spent below (TSB) <70 mg/dL was 9.2%, and TSB <54 mg/dL was 3.7%. The mean area under curve (AUC) <70 mg/dL was 1.7 ± 2.5 mg/dL/hour and AUC <54 mg/dL was 0.6 ± 1.3 mg/dL/hour. All of the CGM-derived hypoglycemic indices were significantly more deranged at night compared with during the day (P < 0.05). CONCLUSION: Patients with diabetes of the exocrine pancreas have a high frequency of hypoglycemic episodes that are predominantly nocturnal. CGM is superior to SMBG in the detection of nocturnal and asymptomatic hypoglycemic episodes. CGM-derived hypoglycemic indices are beneficial in estimating the risk of hypoglycemia.


Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Pancreas, Exocrine , Blood Glucose , Blood Glucose Self-Monitoring , Cross-Sectional Studies , Humans , Hypoglycemia/diagnosis , Hypoglycemic Agents/adverse effects
4.
Diabetes Metab Syndr ; 14(5): 1299-1304, 2020.
Article in English | MEDLINE | ID: mdl-32755825

ABSTRACT

OBJECTIVES: To determine the prevalence of hypogonadism among Indian men with and without type 2 diabetes mellitus (T2DM) and evaluate its association with various metabolic parameters. METHODS: One hundred fifty consecutive men with T2DM, aged 25-70 years, and one hundred age-matched healthy men without diabetes were included. The free testosterone (FT) level was calculated using the total testosterone (TT), sex hormone-binding globulin (SHBG), and albumin levels in serum. Patients with a calculated FT level <6.35 ng/dL and a positive response on the androgen deficiency in aging male questionnaire (ADAM) were diagnosed with hypogonadism. RESULTS: The prevalence of hypogonadism was 17.3% and 10% in men with and without T2DM, respectively. The body mass index (BMI) and the mean levels of follicle-stimulating hormone (FSH), TT, SHBG, Triglycerides (TG), and FT were significantly different between the groups. The mean BMI and TG levels were significantly higher in patients with T2DM than in those without. Both groups showed a significant negative correlation between the BMI and SHBG level. CONCLUSION: The hypogonadism prevalence was higher in patients with T2DM than in those without, although the difference did not reach statistical significance.


Subject(s)
Diabetes Mellitus, Type 2/complications , Hypogonadism/epidemiology , Adult , Aged , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Hypogonadism/blood , Hypogonadism/etiology , Hypogonadism/pathology , India/epidemiology , Middle Aged , Prevalence , Prognosis , Prospective Studies , Surveys and Questionnaires , Testosterone/blood
5.
Diabetes Metab Syndr ; 14(5): 789-795, 2020.
Article in English | MEDLINE | ID: mdl-32531743

ABSTRACT

BACKGROUND AND AIMS: Intra-abdominal adipose tissue (IAAT) is a major contributor to insulin resistance (IR) in type 2 diabetes mellitus (T2D). Prior studies have demonstrated evidence of IR in fibrocalculous pancreatic diabetes (FCPD). However, no data exists on IAAT estimation in FCPD. Hence, we compared IAAT area among FCPD patients and an equal number of body mass index (BMI) matched T2D patients and healthy controls. METHODS: We recruited 60 patients with FCPD between January 2019 and February 2020. Body composition analysis was performed via bio-electrical impedance analysis. RESULTS: The mean ages were 37.82 ± 10.07, 51.02 ± 9.9, and 30.7 ± 11.51 years for patients in the FCPD, T2D, and control groups, respectively. The mean BMI of patients in the three groups was 20.65 ± 2.01, 20.83 ± 1.49, and 20.91 ± 1.59 kg/m2, respectively (P = 0.684). The mean IAAT area of patients in the FCPD, T2D, and control groups was 67.93 ± 43.38, 117.78 ± 48.03, and 100.52 ± 42.31 cm2, respectively. IAAT was significantly lower in patients with FCPD compared with those in the other two groups (P < 0.0001). In the entire cohort, IAAT showed significant positive correlation with age (r = 0.20), abdominal circumference (r = 0.80), waist hip ratio (r = 0.75), and LDL level (r = 0.25) (P < 0.05). CONCLUSIONS: Patients with FCPD have significantly lower IAAT compared to BMI matched T2D subjects and healthy controls. IAAT does not appear to be a major contributor to insulin resistance observed in patients with FCPD.


Subject(s)
Biomarkers/analysis , Diabetes Mellitus, Type 2/diagnosis , Electric Impedance , Insulin Resistance , Intra-Abdominal Fat/pathology , Pancreatic Diseases/diagnosis , Adult , Blood Glucose/analysis , Body Mass Index , Case-Control Studies , Cohort Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2/metabolism , Female , Follow-Up Studies , Humans , Intra-Abdominal Fat/metabolism , Male , Middle Aged , Pancreatic Diseases/metabolism , Prognosis , Waist-Hip Ratio
6.
Acta Diabetol ; 57(9): 1073-1080, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32266492

ABSTRACT

AIM: The present study aimed to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in patients with type 2 diabetes mellitus (T2D). METHODS: We recruited 2887 patients with T2D between January 2018 and November 2019 and categorized them into two groups (metformin and non-metformin users) matched for age, mean duration of diabetes, and BMI. We calculated the "Metformin Usage Index" (MUI) which was defined as the product of the dose of metformin (mg) used and its duration divided by 1000. Vitamin B12 levels were compared between the two groups, and its association with MUI was assessed using correlation and multistep logistic regression analyses. RESULTS: Vitamin B12 levels < 200 pg/ml and between 200 and 300 pg/ml were noted among 24.5% and 34.5% metformin users, respectively; this was significantly higher than among non-metformin users (17.3% and 22.6%, respectively) [P < 0.001]. Overall, a vitamin B12 level < 300 pg/ml was found in 52.2% of the subjects. There was a significant association between an MUI > 5 and a high risk of vitamin B12 deficiency [P < 0.01]. The highest risk was observed among patients with an MUI > 15 [odds ratio (OR) 6.74, 95% CI 4.39-10.4] followed by patients with an MUI > 10 (OR 5.12, 95% CI 3.12-8.38). CONCLUSIONS: The MUI can be employed as a risk assessment tool for evaluation of vitamin B12 deficiency in patients with T2D. Further prospective studies are required to determine the MUI thresholds in populations with good nutritional statuses and low prevalence of vitamin B12 deficiency.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Metformin/administration & dosage , Vitamin B 12 Deficiency/epidemiology , Adult , Case-Control Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Dose-Response Relationship, Drug , Female , Humans , Hypoglycemic Agents/administration & dosage , Male , Middle Aged , Prevalence , Prospective Studies , Risk Assessment , Vitamin B 12/blood , Vitamin B 12 Deficiency/blood , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/diagnosis
7.
Int J Impot Res ; 32(3): 289-296, 2020 May.
Article in English | MEDLINE | ID: mdl-31000814

ABSTRACT

The Androgen Deficiency in the Aging Male (ADAM) questionnaire is commonly used to screen type 2 diabetes mellitus (T2DM) patients for androgen deficiency symptoms, but the association of low total (TT) and free testosterone (FT) levels with divergent responses to the ADAM questionnaire remains unclear. The aim of this study was to assess the predictive ability of TT and calculated FT (cFT) levels for accurately classifying ADAM status. We recruited 70 patients each with positive (group A) and negative (group B) responses to the ADAM questionnaire and 70 age-matched healthy controls (group C) (mean age, 50.5 years); serum levels of TT were estimated and cFT were estimated using Vermeulen equation. Hypogonadism was defined as the presence of symptoms (positive ADAM score) along with TT level < 300 ng/dL or calculated (cFT) <6.35 ng/dL. BMI was highest in group A (P < 0.05), followed by groups B and C. Group A had longer diabetes durations (P < 0.05) and higher fasting plasma glucose (FPG) and HbA1c levels than group B (P < 0.001). TT levels and cFT were significantly lower in Group A than in the other two groups. In group A, 51 (73%) men had low TT levels (<300 ng/dL) and 48 (69%) had low cFT (<6.35 ng/dL). TT levels < 300 ng/dL had higher sensitivity and specificity (73 and 96%, respectively) than cFT < 6.35 ng/dL (69 and 90%, respectively) for predicting ADAM status. Multivariate-adjusted logistic regression showed that diabetes duration, HbA1c level, and BMI predicted low TT levels, whereas diabetes duration and HbA1c and high-density lipoprotein levels were significant predictors of low cFT. TT levels were a better predictor of ADAM responses than cFT in male T2DM patients. Our results suggest that TT level is better than cFT for diagnosing hypogonadism in T2DM patients when equilibrium dialysis is not feasible.


Subject(s)
Diabetes Mellitus, Type 2 , Androgens , Diabetes Mellitus, Type 2/complications , Female , Humans , Hypogonadism/complications , Hypogonadism/diagnosis , Male , Middle Aged , Surveys and Questionnaires , Testosterone
8.
Diabetes Metab Syndr ; 13(2): 1511-1516, 2019.
Article in English | MEDLINE | ID: mdl-31336514

ABSTRACT

AIMS: The present study aimed to compare the clinical characteristics of patients with fibrocalculous pancreatic diabetes (FCPD) and those with type 2 diabetes mellitus (T2DM) to identify the characteristics distinctive of FCPD. METHODS: A total of 133 patients with FCPD were compared with 665 patients with T2DM matched for duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular and macrovascular complications in both groups. RESULTS: The mean duration of diabetes was 4.42 ±â€¯5.65 years in the FCPD group and 4.51 ±â€¯3.88 years in the T2DM group. FCPD participants were significantly younger at diagnosis and leaner than patients with T2DM. The FCPD group had higher fasting and postprandial glucose and HbA1c levels than the T2DM group. The FCPD group had significantly lower triglyceride, total cholesterol, low-density lipoprotein cholesterol, serum total calcium, hemoglobin, and serum creatinine values than the T2DM group. The prevalence of coronary artery disease, stroke, and retinopathy was significantly higher in the T2DM patients while the prevalence of distal symmetric polyneuropathy was significantly lower. On multivariate logistic regression analysis, duration of diabetes and HbA1c (OR = 1.17, P = 0 0.04) in FCPD patients and age (OR = 1.04, P < 0 0.001), duration of diabetes (OR = 1.17, P < 0 0.001) and HbA1c (OR = 1.28, P < 0.001) in T2DM patients were associated with microvascular complications. CONCLUSIONS: There are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM. Timely diagnosis may have implications in the follow-up and management of patients.


Subject(s)
Biomarkers/analysis , Diabetes Complications/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/epidemiology , Pancreatic Diseases/physiopathology , Aged , Blood Glucose/analysis , Diabetes Complications/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Angiopathies/metabolism , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , India/epidemiology , Male , Middle Aged , Pancreatic Diseases/metabolism , Prevalence , Prognosis
9.
Diabetes Metab Syndr Obes ; 12: 779-788, 2019.
Article in English | MEDLINE | ID: mdl-31190936

ABSTRACT

Background: Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes seen in patients with tropical chronic pancreatitis. Insulin deficiency plays a major role in the etiopathogenesis of FCPD. Limited data suggest a possible role of insulin resistance (IR) in the pathogenesis of FCPD. Sparse data exist on measures of insulin sensitivity (IS) and secretion in patients with FCPD and its comparison to type 2 diabetes mellitus (T2D) patients. Method: Eighty patients with FCPD, 36 patients with T2D and 36 healthy subjects were included. A 75 g oral glucose tolerance test (OGTT) was performed in the morning after an overnight fast. We evaluated IS and secretion using indices derived from fasting (homeostasis model assessment of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI] and homeostasis model assessment of beta-cell function [HOMA-ß]) and OGTT (Matsuda, insulin sensitivity index by Kanauchi [ISI-K], oral glucose insulin sensitivity index [OGIS], Stumvoll, insulinogenic index and oral disposition index [ODI]) measurements of glucose and insulin. Results: HOMA-IR was significantly higher and QUICKI significantly lower in patients with FCPD and T2D than in healthy controls (P<0.001). Matsuda, ISI-K, OGIS and Stumvoll were significantly lower in patients with FCPD and T2D than in healthy controls (P<0.001), indicating reduced IS in both FCPD and T2D patients. HOMA-ß, insulinogenic index and ODI were significantly lower in patients with FCPD and T2D compared to healthy controls (P<0.001). Conclusion: FCPD is associated with reduced IS as assessed by fasting and OGTT-based indices. FCPD is also associated with a greater degree of impairment in insulin secretion than in T2D. IR may play a role in the pathogenesis of FCPD.

10.
Pituitary ; 22(1): 4-12, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30317419

ABSTRACT

PURPOSE: Hypopituitarism (HP) is an uncommon consequence of Russell's viper envenomation (RVE). Delayed hypopituitarism (DHP) presents months to years after recovering from snake bites (SB). The clinical presentation, manifestations, and outcomes of DHP following RVE have not been systematically studied. Here, we present a case series of HP following RVE with delayed diagnosis and conduct a literature review. METHODS: We retrospectively reviewed data of eight DHP cases and literature to outline the presentation, manifestations, hormonal profiles, and radiological features of DHP following RVE. RESULTS: Three men and five women, with a mean age at diagnosis of 39.5 ± 11.6 years, were included. The mean duration between snake bite (SB) and HP diagnosis was 8.1 ± 3.6 years. Secondary hypothyroidism and hypogonadotropic hypogonadism were present in all patients. Growth hormone deficiency (GHD) and secondary hypocortisolism were present in 6 (75%) patients. Magnetic resonance imaging (MRI) revealed empty sella and partially empty sella in three patients each (75%). The literature review revealed additional 20 DHP cases (mean age at diagnosis 32.4 ± 10.8 years), with 65% of patients being men. Fatigue, reduced libido, and loss of weight were the commonest symptoms among men. Secondary amenorrhea, fatigue, and loss of appetite were common manifestations among women. Acute kidney injury, GHD, secondary hypothyroidism, hypogonadism, and adrenal insufficiency were reported in 75%, 79%, 95%, 100%, and 85% of patients, respectively. CONCLUSIONS: DHP is an important complication of RVE, and a delay in its diagnosis is associated with significant morbidity. Patients with RVE should be followed up for a long term to identify DHP.


Subject(s)
Daboia , Hypopituitarism/diagnosis , Hypopituitarism/etiology , Adult , Amenorrhea/diagnosis , Amenorrhea/etiology , Animals , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Snake Bites , Viper Venoms/toxicity
11.
Indian J Endocrinol Metab ; 22(4): 520-524, 2018.
Article in English | MEDLINE | ID: mdl-30148101

ABSTRACT

BACKGROUND: For patients indicated for surgical treatment, adequate information about the procedure and its complications is a prerequisite for consent, reassures the patient, and allows them to make a well-informed decision. This prospective randomized study aimed to compare the outcomes of three different methods of explaining the procedure of hemithyroidectomy to patients' satisfaction. MATERIAL AND METHODS: The three different methods for explaining the surgical procedure included a conventional diagram, three-dimensional (3D) thyroid model, and 2-minute animated video. A modified Patient Satisfaction Questionnaire was used to evaluate the efficacy of the methods and assess overall patient experience; 20 patients were randomized to each group. An endocrine surgeon performed the operative procedure using a sutureless technique. The procedure was explained to the patient a week before surgery in the outpatient department. RESULTS: Majority of the patients were female. The most common indication for surgery was a solitary thyroid nodule. Patients who watched the animated video demonstrated significantly higher satisfaction levels and significantly lower anxiety levels than those in the other groups (P < 0.01). Patients who watched the video or who received instructions using the 3D model also reported that their information needs were met. Overall experience with the procedure and hospital stay was not significantly different between the groups. CONCLUSION: Overall patient satisfaction for the surgical procedure was similar across the three groups. However, the animated video appeared to be a better model to explain the procedure to the patient, resulting in enhanced knowledge acquisition, reduced anxiety, and improved patient satisfaction.

12.
BMJ Case Rep ; 20182018 Jul 11.
Article in English | MEDLINE | ID: mdl-30002216

ABSTRACT

The differential diagnosis of a girl presenting with primary amenorrhoea includes numerous conditions. Often, patients of 46XY disorder of sex development (DSD) are reared as girl and present with primary amenorrhoea. Their further evaluation to reach the final diagnosis is often a great challenge. In this article, we report a challenging case of 46XY DSD presented with primary amenorrhoea. Patient had spontaneous breast development which initially confused the diagnosis to complete androgen insensitivity syndrome. However, low testosterone suggested against this possibility and further evaluation revealed hormonal findings consistent with 17α hydroxylase/17,20 lyase (CYP17A1) deficiency. Patient had 46XY karyotype and in consistence with hormonal findings patient was found to have a likely pathogenic homozygous c.1345C>T (p.Arg449Cys) variation in exon 8 of CYP17A1.


Subject(s)
Amenorrhea/diagnosis , Disorder of Sex Development, 46,XY/diagnosis , Amenorrhea/genetics , Androgen-Insensitivity Syndrome/diagnosis , Diagnosis, Differential , Diagnostic Errors , Disorder of Sex Development, 46,XY/genetics , Female , Humans , Male , Steroid 17-alpha-Hydroxylase/genetics , Young Adult
13.
Diabetes Res Clin Pract ; 139: 188-194, 2018 May.
Article in English | MEDLINE | ID: mdl-29524484

ABSTRACT

AIMS: To investigate the factors associated with abnormal electrochemical skin conductance (ESC) in patients with type 2 diabetes mellitus (T2D) and early diabetic peripheral neuropathy (DPN). METHODS: We recruited 523 consecutive patients with T2D (median age: 50 [interquartile range: 16] years; median T2D duration: 4 [5] years). Sudomotor dysfunction was defined as an ESC <60 µS, and DPN as a neuropathy disability score (NDS) ≥6. Logistic regression was performed to determine the predictors of sudomotor dysfunction in patients with DPN. RESULTS: The prevalence of sudomotor dysfunction was 29% for all patients and 84.5% for patients with DPN. A significant negative correlation was observed between the NDS and ESC measurements (r = -0.52, p < 0.0001). In the univariate analysis, abnormal ESC measures were associated with age, diabetes duration, glycated hemoglobin, diabetic retinopathy, insulin therapy, and foot abnormalities. In the multivariate analysis, ESC abnormalities were associated with age, diabetes duration, glycated hemoglobin levels, insulin therapy, and foot deformities. There was a robust association between foot deformities and abnormal ESC (p = 0.049; odds ratio = 16.02) in patients with DPN. CONCLUSION: Sudomotor dysfunction is highly prevalent in patients with T2D, especially in those with DPN. Various diabetes-related factors were linked to lower ESC values, indicating an association between chronic hyperglycemia and sudomotor function. We also observed a strong relationship between foot deformities and ESC abnormalities. We conclude that the factors associated with DPN are also relevant to sudomotor dysfunction.


Subject(s)
Autonomic Nervous System/physiopathology , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/physiopathology , Small Fiber Neuropathy/physiopathology , Diabetes Mellitus, Type 2/pathology , Female , Humans , Male , Middle Aged
14.
PLoS One ; 12(9): e0183973, 2017.
Article in English | MEDLINE | ID: mdl-28880907

ABSTRACT

The early diagnosis of diabetic peripheral neuropathy (DPN) is challenging. Sudomotor dysfunction is one of the earliest detectable abnormalities in DPN. The present study aimed to determine the diagnostic performance of the electrochemical skin conductance (ESC) test in detecting early DPN, compared with the vibration perception threshold (VPT) test and diabetic neuropathy symptom (DNS) score, using the modified neuropathy disability score (NDS) as the reference standard. Five hundred and twenty-three patients with type 2 diabetes underwent an NDS-based clinical assessment for neuropathy. Participants were classified into the DPN and non-DPN groups based on the NDS (≥ 6). Both groups were evaluated further using the DNS, and VPT and ESC testing. A receiver-operator characteristic (ROC) curve analysis was performed to compare the efficacy of ESC measurements with those of DNS and VPT testing in detecting DPN. The DPN group (n = 110, 21%) had significantly higher HbA1c levels and longer diabetes durations compared with the non-DPN group (n = 413). The sensitivity of feet ESC < 60 µS, VPT testing, and DNS in detecting DPN were 85%, 72%, and 52%, respectively. The specificity of feet ESC, VPT, and DNS in detecting DPN were 85%, 90% and 60% respectively. The areas under the curves of the ROC plots for feet ESC, VPT testing, and DNS were 0.88, 0.84, and 0.6, respectively. A significant inverse linear relationship was noted between VPT and feet ESC (r = -0.45, p = <0.0001). The odds ratios for having DPN, based on the mean feet ESC testing < 60 µS, VPT testing > 15 V, and DNS ≥ 1, were 16.4, 10.9 and 1.8, respectively. ESC measurement is an objective and sensitive technique for the early detection of DPN. Feet ESC measurement was superior to VPT testing for identifying patients with early DPN.


Subject(s)
Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/physiopathology , Galvanic Skin Response , Perception , Sensory Thresholds , Vibration , Confidence Intervals , Female , Humans , Male , Middle Aged , Odds Ratio , ROC Curve
15.
J Pediatr Endocrinol Metab ; 30(7): 707-712, 2017 Jul 26.
Article in English | MEDLINE | ID: mdl-28672742

ABSTRACT

BACKGROUND: Type 1 diabetes (T1D) is frequently associated with other autoimmune conditions such as autoimmune thyroiditis, coeliac disease (CD) and Addison's disease. There are sparse data on the prevalence of antibodies against these conditions in Indian patients with T1D. This study aims to evaluate prevalence of these T1D associated autoantibodies in Indian patients. METHODS: Two hundred and fifty-eight patients with T1D were recruited from the Bangalore Diabetes Hospital and the Vydehi Institute of Medical Sciences and Research Centre (VIMS) for the study. Participants diagnosed with diabetes before the age of 18 years, as per the American Diabetes Association (ADA) criteria, and who were classified as T1D based on clinical grounds were recruited for the study. Anti-thyroid peroxidase antibody (TPO) and IgA tissue transglutaminase antibody (tTG) were estimated in all the patients. 21-Hydroxylase antibody (21-OHAb) were estimated in 170 patients. All assays were done by commercial immunoassay. Eighty-eight unrelated age-matched healthy controls were chosen for comparison. RESULTS: The mean age of T1D patients was 14.33 years. The mean duration of diabetes was 4.88 years. Anti-TPO was positive in 43 (16.7%) patients with T1D as compared to 3 (3.4%) in controls. IgA tTG was positive in 12 (4.65%) patients with T1D and was absent in controls. 21-OHAb was positive in two (1.1%) patients with T1D and was absent in controls. Both patients who had positive 21-OHab had the other two antibodies. Five patients had positive anti-TPO and IgA-tTG antibodies. CONCLUSIONS: Anti-TPO antibody was the most prevalent antibody in patients with T1D. Anti-TPO and IgA-tTG antibodies were significantly higher than in the control population. Further studies will be required to assess the clinical significance of these positive antibodies.


Subject(s)
Autoantibodies/blood , Autoimmune Diseases/blood , Diabetes Mellitus, Type 1/immunology , Adolescent , Autoantibodies/immunology , Autoimmune Diseases/epidemiology , Autoimmune Diseases/etiology , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 1/complications , Female , Follow-Up Studies , Humans , India/epidemiology , Male , Organ Specificity , Prevalence , Prognosis
16.
J Pediatr Endocrinol Metab ; 26(7-8): 695-702, 2013.
Article in English | MEDLINE | ID: mdl-23612636

ABSTRACT

There are few large-scale studies on the utility of peripheral dual energy X-ray absorptiometry (pDXA) in children. As central dual energy X-ray absorptiometry (cDXA) equipment is not commonly available in the developing world, we assessed the correlation of bone mineral density (BMD) with cDXA and pDXA in children to determine the optimal Z-score thresholds of pDXA for predicting two predefined Z-score cutoffs (≤-1, ≤-2) of cDXA in 844 subjects (441 boys, 403 girls) aged 10-18 years. The BMD of antero-posterior lumbar spine (L1-L4), proximal femur and forearm was measured by cDXA, while the peripheral BMD of forearm and calcaneus was estimated using pDXA. The correlation was statistically significant at all sites (p<0.01). The coefficients ranged from 0.56 to 0.79 in boys and 0.17 to 0.32 in girls. A significant positive correlation was observed between BMD by pDXA and cDXA in Indian children, with a strong gender difference in both the extent of correlation and the ability of peripheral BMD to predict central BMD.


Subject(s)
Absorptiometry, Photon/methods , Bone Density , Adolescent , Child , Female , Humans , Male
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